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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Oncol.</journal-id>
<journal-title>Frontiers in Oncology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Oncol.</abbrev-journal-title>
<issn pub-type="epub">2234-943X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fonc.2024.1275009</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Oncology</subject>
<subj-group>
<subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Circ_0003945: an emerging biomarker and therapeutic target for human diseases</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Zhang</surname>
<given-names>Xiaofei</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn003">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2599417"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Ma</surname>
<given-names>Li</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn003">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2137511"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Wan</surname>
<given-names>Li</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn003">
<sup>&#x2020;</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Wang</surname>
<given-names>Haoran</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="author-notes" rid="fn003">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2626493"/>
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<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Wang</surname>
<given-names>Zhaoxia</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/869627"/>
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</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University</institution>, <addr-line>Nanjing</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Oncology, The Affiliated Huai&#x2019;an No.1 People&#x2019;s Hospital of Nanjing Medical University</institution>, <addr-line>Huai&#x2019;an</addr-line>, <country>China</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Division of Spine Surgery, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine</institution>, <addr-line>Shanghai</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Mantang Qiu, Peking University People&#x2019;s Hospital, China</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Rana A. Youness, German International University, Egypt</p>
<p>Zhaowu Ma, Yangtze University, China</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Zhaoxia Wang, <email xlink:href="mailto:wangzhaoxia@njmu.edu.cn">wangzhaoxia@njmu.edu.cn</email>
</p>
</fn>
<fn fn-type="equal" id="fn003">
<p>&#x2020;These authors have contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>22</day>
<month>04</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>14</volume>
<elocation-id>1275009</elocation-id>
<history>
<date date-type="received">
<day>09</day>
<month>08</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>29</day>
<month>03</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Zhang, Ma, Wan, Wang and Wang</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Zhang, Ma, Wan, Wang and Wang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>Due to the rapid development of RNA sequencing techniques, a circular non-coding RNA (ncRNA) known as circular RNAs (circRNAs) has gradually come into focus. As a distinguished member of the circRNA family, circ_0003945 has garnered attention for its aberrant expression and biochemical functions in human diseases. Subsequent studies have revealed that circ_0003945 could regulate tumor cells proliferation, migration, invasion, apoptosis, autophagy, angiogenesis, drug resistance, and radio resistance through the molecular mechanism of competitive endogenous RNA (ceRNA) during tumorigenesis. The expression of circ_0003945 is frequently associated with some clinical parameters and implies a poorer prognosis in the majority of cancers. In non-malignant conditions, circ_0003945 also holds considerable importance in diseases pathogenesis. This review aims to recapitulate molecular mechanism of circ_0003945 and elucidates its potential as a diagnostic and therapeutic target in neoplasms and other diseases.</p>
</abstract>
<kwd-group>
<kwd>cancer</kwd>
<kwd>circ_0003945</kwd>
<kwd>ceRNA</kwd>
<kwd>biomarker</kwd>
<kwd>therapeutic target</kwd>
</kwd-group>
<contract-sponsor id="cn001">National Natural Science Foundation of China<named-content content-type="fundref-id">10.13039/501100001809</named-content>
</contract-sponsor>
<counts>
<fig-count count="4"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="115"/>
<page-count count="16"/>
<word-count count="5494"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Molecular and Cellular Oncology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>Cancer represents a serious public health issue that affects people all around the world (<xref ref-type="bibr" rid="B1">1</xref>). Various etiological factors and socioeconomic elements including population aging exacerbate the cancer burden and contributing to an increase in cancer-related fatalities (<xref ref-type="bibr" rid="B2">2</xref>). Despite the availability of cutting-edge medical diagnostics and therapeutics, recurrence and metastasis still pose dramatic barriers to achieving long-term survival in patients (<xref ref-type="bibr" rid="B3">3</xref>&#x2013;<xref ref-type="bibr" rid="B5">5</xref>).</p>
<p>CircRNAs, a new class of non-coding RNA (ncRNA) distinct from traditional linear RNAs, are characterized by their covalently closed, continuous loop structures (<xref ref-type="bibr" rid="B6">6</xref>). First identified in plants viroids in 1976 (<xref ref-type="bibr" rid="B7">7</xref>), circRNAs were subsequently detected in eukaryotic cells in 1979 (<xref ref-type="bibr" rid="B8">8</xref>). The discovery that the hepatitis delta virus (HDV) has a single-stranded circRNA molecule marked it as the first known animal virus with a circRNA genome in 1986 (<xref ref-type="bibr" rid="B9">9</xref>). Specifically, circRNA is generated by the RNA polymerase II (pol II)&#x2013;mediated back-splicing of pro-mRNA (<xref ref-type="bibr" rid="B10">10</xref>). Back-splicing forms a stable closed-loop structure devoid of 3&#x2019; or 5&#x2019; end. It restrains the exonuclease-mediated degradation due to its covalent bonding of downstream and upstream splice-donor sites (<xref ref-type="bibr" rid="B11">11</xref>). The nucleotide (nt) length of circRNAs typically ranges from several hundred to a few thousand, and it generally composed of one to five exons (<xref ref-type="bibr" rid="B12">12</xref>). Depending on their splicing sources, circRNAs can be categorized into single-exonic circRNAs, exonic circRNAs (EcircRNAs), intronic circRNAs (CiRNAs), exon&#x2013;intron circRNAs (EIciRNAs), even tRNA intron cirRNAs (tricRNAs) according to their splicing sources (<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>) (<xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B15">15</xref>). CircRNAs are widely expressed in eukaryotes, where EcircRNAs are predominantly localized in the cytoplasm, while EcircRNAs and EIciRNAs are primarily nucleus (<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B17">17</xref>). In summary, circRNAs demonstrates tissue-specific localization and evolutionary conservation, stably persisting in intricate intracellular and extracellular environments, holding promise as ideal tumor biomarkers (<xref ref-type="bibr" rid="B18">18</xref>, <xref ref-type="bibr" rid="B19">19</xref>). CircRNAs perform various biological functions (<xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2</bold>
</xref>): (1) as endogenous RNAs (ceRNA), circRNAs act as molecular sponges, impeding the microRNA (miRNA)&#x2013;mediated repression of target genes (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>). (2) CircRNAs serve as molecular sponges for proteins, particularly RNA-binding proteins, regulating the transcription or translation of downstream target genes (<xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B23">23</xref>). (3) CircRNAs function as protein scaffolds facilitating interactions between specific proteins (<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B24">24</xref>). (4) CircRNAs possess translational capacity, producing peptides that exert biological functions (<xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>). (5) CircRNAs maintain the stability of mRNA and regulate its translation, facilitating or inhibiting the respective translation processes (<xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B28">28</xref>). (6) EIciRNAs and CiRNAs have been identified to be transcription regulators. EIciRNA locating in the nuclear can interact with the U1 small nuclear ribonucleoprotein (snRNP) and bind to RNA pol II, enhancing the transcription of their host genes. CiRNAs also modulate RNA pol II&#x2013;mediated transcription, exerting a cis-regulatory effect on upstream genes (<xref ref-type="bibr" rid="B29">29</xref>). CircRNAs can directly bind with nuclear transcription factors (TFs) to regulate their activity and function (<xref ref-type="bibr" rid="B30">30</xref>). Additionally, the transcription of some circRNAs might occur independently of host genes, regulated by TFs, as opposed to the general assumption of deriving from host transcript splicing (<xref ref-type="bibr" rid="B31">31</xref>). For instance, a set of circRNAs with transcription activation levels higher than those of host genes, identified as transcriptionally activated to a higher level than the host genes (TAH)-circRNAs, exhibited more TFs occupancy in their regulatory regions. Certain TFs, especially the validated super&#xa0;enhancer (SE) FOXA1 validated already, directly regulated the transcription of TAH-circRNAs (<xref ref-type="bibr" rid="B32">32</xref>, <xref ref-type="bibr" rid="B33">33</xref>). A novel genetic unit, the intragenic regulon (iRegulon), also differently regulates the expression of linear and circular RNA products, thereby&#xa0;manifesting distinct biological functions (<xref ref-type="bibr" rid="B30">30</xref>). To date, circRNAs have been established as participants in variety of physiopathological processes (<xref ref-type="bibr" rid="B14">14</xref>).</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Biogenesis of circRNAs.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1275009-g001.tif"/>
</fig>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>Functions and mechanisms of circRNAs in eukaryotes. <bold>(A)</bold> Acting as miRNA sponge; <bold>(B)</bold> acting as protein sponge and scaffold; <bold>(C)</bold> acting as templates for translation; <bold>(D)</bold> maintaining mRNA stability and regulate translation; <bold>(E)</bold> regulating transcription.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1275009-g002.tif"/>
</fig>
<p>Circ_0003945 (circBase ID: hsa_circ_0003945) was located on chr9: 33953282&#x2013;33956144, with a total length of 258 nt. It was formed by back-spliced of the 11 and 12 exons of the ubiquitin-associated protein 2 (UBAP2) and aliased hsa_circ_0001846 (<xref ref-type="bibr" rid="B34">34</xref>), hsa_circ_0001850 (<xref ref-type="bibr" rid="B35">35</xref>), hsa_circ_0003141 (<xref ref-type="bibr" rid="B36">36</xref>), hsa_circ_0003496 (<xref ref-type="bibr" rid="B37">37</xref>), hsa_circ_0007367 (<xref ref-type="bibr" rid="B38">38</xref>), hsa_circ_0008344 (<xref ref-type="bibr" rid="B39">39</xref>), and hsa_circ_0086735 (<xref ref-type="bibr" rid="B40">40</xref>) (<xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>). For the sake of narrative clarity in this text, it will be uniformly referred to as circ_0003945. Studies have confirmed that circ_0003945 showed resistance to digestion by ribonuclease R (RNase R), whereas the corresponding linear transcript was considerable diminished after RNase R treatment, underscoring the stability of its covalently closed-loop structures (<xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B43">43</xref>). Circ_0003945 have been associated with a variety of diseases, including various neoplasms and non-malignant conditions such as microcirculatory perfusion (<xref ref-type="bibr" rid="B44">44</xref>, <xref ref-type="bibr" rid="B45">45</xref>), diabetic retinopathy (DR) (<xref ref-type="bibr" rid="B35">35</xref>), osteoarthritis (OA) (<xref ref-type="bibr" rid="B46">46</xref>), preeclampsia (PE) (<xref ref-type="bibr" rid="B47">47</xref>), and milk fat metabolism (<xref ref-type="bibr" rid="B48">48</xref>). Noteworthy, circ_0003945 was highly overexpressed and linked to poor prognosis, including in glioma (<xref ref-type="bibr" rid="B49">49</xref>), thyroid cancer (TC) (<xref ref-type="bibr" rid="B36">36</xref>), esophageal cancer (EC) (<xref ref-type="bibr" rid="B50">50</xref>), non-small cell lung cancer (NSCLC) (<xref ref-type="bibr" rid="B51">51</xref>), breast cancer (BC) (<xref ref-type="bibr" rid="B34">34</xref>), hepatocellular carcinoma (HCC) (<xref ref-type="bibr" rid="B52">52</xref>), pancreatic cancer (<xref ref-type="bibr" rid="B53">53</xref>), colorectal cancer (CRC) (<xref ref-type="bibr" rid="B54">54</xref>), ovarian cancer (OC) (<xref ref-type="bibr" rid="B55">55</xref>), cervical cancer (CC) (<xref ref-type="bibr" rid="B56">56</xref>), prostate cancer (<xref ref-type="bibr" rid="B57">57</xref>), and osteosarcoma (<xref ref-type="bibr" rid="B58">58</xref>) (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>). However, it is noteworthy that the expression of circ_0003945 in gastric cancer (GC) (<xref ref-type="bibr" rid="B59">59</xref>) and renal cell carcinoma (RCC) (<xref ref-type="bibr" rid="B60">60</xref>) were lower compared to normal tissue, which also suggested a more favorable prognosis. Additionally, circ_0003945 was implicated in the regulation of tumor cell proliferation, migration, invasion, apoptosis, drug resistance, and radio resistance (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>) and correlated with the clinicopathological characteristics of tumor patients (<xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>). This review will synthesize the potential molecular mechanisms by which circ_0003945 driven tumorigenesis and its clinical significance in human diseases.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Alias of circ_0003945 and different splicing methods from UBAP2 gene in diseases.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">CircRNA ID</th>
<th valign="top" align="left">Position</th>
<th valign="top" align="left">Genomic length (nt)</th>
<th valign="top" align="left">Spliced sequence length (nt)</th>
<th valign="top" align="left">Involving disease</th>
<th valign="top" align="left">Ref.</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">hsa_circ_0001846 (alias hsa_circ_1335)</td>
<td valign="top" align="left">chr9:33944362-33956144</td>
<td valign="top" align="left">11782</td>
<td valign="top" align="left">747</td>
<td valign="top" align="left">BC, prostate cancer, OA</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">34</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_0001850<break/>(alias hsa_circ_1782)</td>
<td valign="top" align="left">chr9:33960823-33973235</td>
<td valign="top" align="left">12412</td>
<td valign="top" align="left">278</td>
<td valign="top" align="left">DR</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B35">35</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_0003141</td>
<td valign="top" align="left">chr9:33953282-33973235</td>
<td valign="top" align="left">19953</td>
<td valign="top" align="left">536</td>
<td valign="top" align="left">TC</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_0003496</td>
<td valign="top" align="left">chr9:33948371-33953472</td>
<td valign="top" align="left">5101</td>
<td valign="top" align="left">404</td>
<td valign="top" align="left">Osteosarcoma, PE</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_0003945</td>
<td valign="top" align="left">chr9:33953282-33956144</td>
<td valign="top" align="left">2862</td>
<td valign="top" align="left">258</td>
<td valign="top" align="left">HCC</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">41</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_0007367</td>
<td valign="top" align="left">chr9:33948371-33956144</td>
<td valign="top" align="left">7773</td>
<td valign="top" align="left">472</td>
<td valign="top" align="left">Pancreatic cancer, cardiogenic shock</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B38">38</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_0008344</td>
<td valign="top" align="left">chr9:33935836-33941860</td>
<td valign="top" align="left">6024</td>
<td valign="top" align="left">254</td>
<td valign="top" align="left">Glioma</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B39">39</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">hsa_circ_00086735</td>
<td valign="top" align="left">chr9:33986757-34017187</td>
<td valign="top" align="left">30430</td>
<td valign="top" align="left">561</td>
<td valign="top" align="left">CRC</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B40">40</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>The expression of circ_0003945 in human tumors.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1275009-g003.tif"/>
</fig>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Functional characterization of circ_0003945 in tumors and non-tumor conditions.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Tumor types</th>
<th valign="top" align="left">Expression</th>
<th valign="top" align="left">Role</th>
<th valign="top" align="left">Assessed tumor cell lines</th>
<th valign="top" align="left">Function roles</th>
<th valign="top" align="left">Animal studies</th>
<th valign="top" align="left">Related genes</th>
<th valign="top" align="left">Ref.</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Glioblastoma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">U87, U251</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B49">49</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Glioma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">U251, LN229</td>
<td valign="top" align="left">Proliferation<break/>Apoptosis<break/>Radio resistance</td>
<td valign="top" align="left">Male BALB/c nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-433-3p, RNF2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B61">61</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Glioma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">U251</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis</td>
<td valign="top" align="left">Female BALB/c mice: tumor volume, weight</td>
<td valign="top" align="left">miR-1205, miR-382, GPRC5Ak</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B62">62</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Glioma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">U251, A172</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Angiogenesis</td>
<td valign="top" align="left">Male BALB/c nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-638, SZRD1</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B39">39</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Papillary thyroid cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">TPC-1, IHH-4</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-370-3p, PI3K/Akt and Wnt pathways</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B63">63</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Esophageal squamous cell carcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">TE-9</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion</td>
<td valign="top" align="left">BALB/C nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-422a, Rab10</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B50">50</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Lung adenocarcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">A549</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>Metastasis<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-339-5, miR-96-3p, miR-135b-3p, JNK-MAPK pathway, Rac1-FAK pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">51</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Non-small cell lung cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">NCI -H1299, A549</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Chemo resistance</td>
<td valign="top" align="left">Female BALB/c nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-3182, KLF4</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B43">43</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Triple-negative breast cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">BT-20, MDA-MB-231</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Metastasis<break/>Apoptosis</td>
<td valign="top" align="left">Female BALB/c nude mice: tumor volume, weight, lung metastasis</td>
<td valign="top" align="left">miR-661, MTA1</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">34</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Triple-negative breast cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">BT-549/DDP, MDA-MB-436/DDP</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis<break/>Cisplatin resistance</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-300, ASF1B, PI3K/AKT/mTOR pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B64">64</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Luminal breast cancer</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">MCF7, ZR-75-1</td>
<td valign="top" align="left">Proliferation<break/>Apoptosis<break/>Tamoxifen resistance</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-1296-5p, STAT1,</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B65">65</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">Huh-7, Hep3B2.1-7</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>Apoptosis<break/>EMT</td>
<td valign="top" align="left">BALB/c nude mice: tumor volumes, weights</td>
<td valign="top" align="left">miR-1827, UBAP2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B52">52</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">HA22T, Huh7</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Metastasis</td>
<td valign="top" align="left">male nude mice: tumor volume, weight, lung metastasis</td>
<td valign="top" align="left">miR-194-3p</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">42</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">MHCC97H, HCCLM3, Li-7</td>
<td valign="top" align="left">Proliferation<break/>Migration</td>
<td valign="top" align="left">Male BALB/c nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-34c-5p, LGR4, wnt/&#x3b2;-catenin pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">41</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">MHCC97H, HCCLM3</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>EMT<break/>Apoptosis</td>
<td valign="top" align="left">NOG mice: tumor volume, weight</td>
<td valign="top" align="left">miR-1294, c-Myc</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B66">66</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">MHCC-97H, Huh-7</td>
<td valign="top" align="left">Migration Invasion</td>
<td valign="top" align="left">BALB/c nude male mice: tumor volume, weight, lung metastasis</td>
<td valign="top" align="left">CXCL11, miR-4756, IFIT1/3</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B67">67</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Pancreatic adenocarcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">Immune infiltration</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-494, CXCR4, ZEB1, SDC1, HIF1A</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B53">53</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Pancreatic ductal adenocarcinoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">AsPC-1, PANC-1</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion</td>
<td valign="top" align="left">BALB/c nude mice: tumor volume, weights</td>
<td valign="top" align="left">Mir-6820-3p, YAP1</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B38">38</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Colorectal cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">SW620, HCT116</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>Migration</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-199a, VEGFA</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B54">54</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Colorectal cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">HCT116, SW480</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>Migration<break/>Metastasis</td>
<td valign="top" align="left">Female BALB/c nude mice: tumor size, weight, lung metastasis</td>
<td valign="top" align="left">miR-582-5p, FOXO1</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B40">40</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Ovarian cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">OVCAR3, HO8910</td>
<td valign="top" align="left">Proliferation<break/>Migration</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-144, CHD2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B55">55</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Ovarian cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">OVCAR-3, ES-2</td>
<td valign="top" align="left">Proliferation<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-382-5p, PRPF8</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B68">68</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Cervical cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">HeLa, SiHa</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Metastasis<break/>EMT<break/>Apoptosis</td>
<td valign="top" align="left">BALB/c nude mice: tumor volumes, weight, lung metastasis</td>
<td valign="top" align="left">miR-361-3p, SOX4</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B56">56</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Prostate cancer</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">LNCaP, V16A, DU145, PC-3</td>
<td valign="top" align="left">Proliferation</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-1244, MAP3K2, MAPK pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B57">57</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">MG63, U2OS</td>
<td valign="top" align="left">Proliferation<break/>Apoptosis</td>
<td valign="top" align="left">BALB/c athymic nude mice: tumor volume</td>
<td valign="top" align="left">miR-143, Bcl-2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B58">58</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">U2OS, SaOS2</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>EMT</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-641, YAP1</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B69">69</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">U2OS/CDDP, SaOS-2/CDDP</td>
<td valign="top" align="left">Proliferation<break/>Invasion<break/>Migration<break/>Apoptosis<break/>Cisplatin resistance</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-506-3p, SEMA6D, Wnt/&#x3b2;-catenin pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B70">70</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Upregulate</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">KHOS/DXR, MG63/DXR</td>
<td valign="top" align="left">Proliferation Migration<break/>Invasion<break/>Apoptosis<break/>DXR Sensitivity</td>
<td valign="top" align="left">BALC/c nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-370, KLF12</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">HOS, SaOS-2</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-204-3p, HMGA2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B71">71</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">SaOS-2, HOS</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis</td>
<td valign="top" align="left">Male nude mice: tumor volume, weight</td>
<td valign="top" align="left">miR-637, HMGB2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B72">72</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Gastric cancer</td>
<td valign="top" align="left">Downregulation</td>
<td valign="top" align="left">Suppressor gene</td>
<td valign="top" align="left">SGC-7901/CDDP, MKN-45/CDDP</td>
<td valign="top" align="left">Proliferation<break/>Apoptosis<break/>Cisplatin resistance</td>
<td valign="top" align="left">Male BALB/c mice: tumor volume, weight</td>
<td valign="top" align="left">miR-300, KAT6B</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B59">59</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Clear cell renal cell carcinoma</td>
<td valign="top" align="left">Downregulated</td>
<td valign="top" align="left">Suppressor gene</td>
<td valign="top" align="left">786-O, A498, ACHN, Caki-1</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-148a-3p, FOXK2</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B60">60</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Microcirculatory perfusion</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">PMVECs</td>
<td valign="top" align="left">Arterial pulsatility</td>
<td valign="top" align="left">Beagles</td>
<td valign="top" align="left">ZO-1, occludin, eNOS, NF-&#x3ba;B pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B44">44</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Microcirculatory perfusion</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">TNF-&#x3b1;, IL-1&#x3b2;, MCP-1, PI3K/Akt/mTOR pathway</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B45">45</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Diabetic retinopathy</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">hRMECs</td>
<td valign="top" align="left">Viability<break/>Migration<break/>Tube formation</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR589-5p, EGR1</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B35">35</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteoarthritis</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">CHON-001</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Invasion<break/>Apoptosis<break/>Inflammation</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-149-5p, WNT5B, IL-1&#x3b2;</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B46">46</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Preeclampsia</td>
<td valign="top" align="left">Downregulated</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">HTR-8/SVneo, JEG-3</td>
<td valign="top" align="left">Proliferation<break/>Migration<break/>Apoptosis</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">miR-1244, FOXM1,</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B47">47</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Milk fat metabolism</td>
<td valign="top" align="left">Upregulated</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">BMEC</td>
<td valign="top" align="left">&#x2013;</td>
<td valign="top" align="left">Dairy cows</td>
<td valign="top" align="left">miR-331-3p</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B48">48</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T3" position="float">
<label>Table&#xa0;3</label>
<caption>
<p>Clinicopathological parameters of circ_0003945 in various cancers.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Tumor types</th>
<th valign="top" align="left">Role</th>
<th valign="top" align="left">Sample size of tumor tissue</th>
<th valign="top" align="left">Clinicopathological feathers</th>
<th valign="top" align="left">Statistical analysis</th>
<th valign="top" align="left">Ref.</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Glioma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">40</td>
<td valign="top" align="left">Overall survival (OS)</td>
<td valign="top" align="left">Kaplan&#x2013;Meier survival analysis with the log-rank test</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B61">61</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Papillary thyroid cancer</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">26</td>
<td valign="top" align="left">Lymph node metastasis</td>
<td valign="top" align="left">Fisher&#x2019;s exact test</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B63">63</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Non-small cell lung cancer</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">60</td>
<td valign="top" align="left">TNM stage, lymph node metastasis</td>
<td valign="top" align="left">Chi-square test</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B43">43</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Triple-negative breast cancer</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">78</td>
<td valign="top" align="left">Tumor size, TNM stage, lymph node metastasis, OS</td>
<td valign="top" align="left">Chi-square test, Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">34</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Luminal breast cancer</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">87</td>
<td valign="top" align="left">Histological type, tumor grade, molecular phenotype, OS, distant, metastasis-free survival (DMFS)</td>
<td valign="top" align="left">Chi-square test, Kaplan&#x2013;Meier analysis with the log-rank test, Multivariate Cox proportional hazards analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B65">65</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">369</td>
<td valign="top" align="left">OS</td>
<td valign="top" align="left">Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B52">52</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">30</td>
<td valign="top" align="left">Tumor size, tumor recurrence rate, OS, recurrence-free survival (RFS)</td>
<td valign="top" align="left">Chi-squared test, Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">42</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">50</td>
<td valign="top" align="left">Tumor size, China liver cancer stage</td>
<td valign="top" align="left">Chi-square test</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">41</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Hepatocellular carcinoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">20</td>
<td valign="top" align="left">Microvascular invasion, differentiation, OS, time to recurrence (TTR)</td>
<td valign="top" align="left">Chi-square test, Kaplan&#x2013;Meier survival analysis, univariate and multivariate Cox proportional regression analyses</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B66">66</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Pancreatic adenocarcinoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">126</td>
<td valign="top" align="left">OS</td>
<td valign="top" align="left">Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B53">53</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Pancreatic ductal adenocarcinoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">128</td>
<td valign="top" align="left">Histological grade, lymph node metastasis, OS</td>
<td valign="top" align="left">Chi-square test, Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B38">38</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Ovarian cancer</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">24</td>
<td valign="top" align="left">TNM stage, 5-year survival rate</td>
<td valign="top" align="left">Chi-square test, Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B55">55</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Cervical cancer</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">58</td>
<td valign="top" align="left">OS</td>
<td valign="top" align="left">Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B56">56</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">92</td>
<td valign="top" align="left">Tumor stage, OS</td>
<td valign="top" align="left">Spearman&#x2019;s rank correlation assay, Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B58">58</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">42</td>
<td valign="top" align="left">TNM stage, distant metastasis, survival rate</td>
<td valign="top" align="left">Chi-square test, Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B71">71</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Osteosarcoma</td>
<td valign="top" align="left">Oncogene</td>
<td valign="top" align="left">40</td>
<td valign="top" align="left">Distant metastasis, TNM stage</td>
<td valign="top" align="left">Chi-square test</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B72">72</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Gastric cancer</td>
<td valign="top" align="left">Suppressor gene</td>
<td valign="top" align="left">63</td>
<td valign="top" align="left">OS</td>
<td valign="top" align="left">Kaplan&#x2013;Meier survival analysis</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B59">59</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s2">
<label>2</label>
<title>The biological functions and mechanisms of circ_0003945 in tumors</title>
<sec id="s2_1">
<label>2.1</label>
<title>Biological functions of circ_0003945 in tumor cells</title>
<p>The expression of circ_0003945 was markedly elevated in tumor cell lines compared to the corresponding normal controls by quantitative real-time polymerase chain reaction (qRT-PCR) and statistical analysis of databases. Intriguingly, in gastric cancer and renal cell carcinoma cell lines, there was an aberrant downregulation of circ_0003945. The regulatory role of circ_0003945 in biological functions of tumor cells and potential mechanisms are as follows (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>).</p>
<sec id="s2_1_1">
<label>2.1.1</label>
<title>Proliferation and cell cycle</title>
<p>Cancer cells exhibit distinct metabolic processes compared to normal cells, characterized by reduced oxidative phosphorylation or abnormal aerobic glycolysis, which drive their growth and proliferation (<xref ref-type="bibr" rid="B73">73</xref>). Employing techniques involving cell counting Kit-8 (CCK-8), ethylenediurea (EDU), or colony formation assay, researchers have uncovered that the overexpression of circ_0003945 enhanced proliferation across mostly tumors cell lines (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>). The MAPK pathway comprises four primary branches: ERK, JNK, p38/MAPK, and ERK5, each playing a crucial role in the cells proliferation, differentiation, migration, and invasion of cancer cells (<xref ref-type="bibr" rid="B74">74</xref>). Notably, the upregulation of circ_0003945 suppressed mircoRNA (miR)&#x2013;1244 and activated MAP3K2 and MAPK key factors (including ERK, JNK, and p38), thereby augmenting the proliferation of prostate cancer cells (<xref ref-type="bibr" rid="B57">57</xref>). Circ_0003945 knockdown reduced the proliferation marker proliferating cell nuclear antigen (PCNA) by performing as an miR-638 sponge. This action effectively sequestered miR-638 from SZRD1, resulting in restrain of glioma cell proliferation (<xref ref-type="bibr" rid="B39">39</xref>).</p>
<p>Deviation in the cell cycle progression is fundamental to tumor cell proliferation. The proceeding of the cell cycle is regulated by&#xa0;metabolic enzymes and upstream regulators, primarily through&#xa0;cyclin-dependent kinases (CDKs) and other critical regulators like APC/C or SCF E3 ligase complexes (<xref ref-type="bibr" rid="B75">75</xref>). Knockdown of circ_0003945 could block the progression of lung adenocarcinoma cells from the G1 to S phase by regulating the binding of p27 to the cyclin-CDK complex. This intervention led to cell cycle to arrest at G0/G1 phase, consequently diminishing cell proliferation <italic>in vitro (</italic>
<xref ref-type="bibr" rid="B51">51</xref>). This mirrored the function of circ_0003945 in glioma (<xref ref-type="bibr" rid="B62">62</xref>) and OC (<xref ref-type="bibr" rid="B68">68</xref>). Conversely, the upregulation of circ_0003945, acting as a tumor suppressor gene, impeded cell cycle in the G1 phase in clear cell RCC cells (<xref ref-type="bibr" rid="B60">60</xref>). Ki-67 acts as specific biomarker of cellular proliferation, regulated through cell cycle-dependent transcription and protein degradation processes (<xref ref-type="bibr" rid="B76">76</xref>, <xref ref-type="bibr" rid="B77">77</xref>). Notably, overexpression of circ_0003945 was significantly associated with enhanced cellular of Ki-67 levels in NSCLC and HCC cells, implicating its roles in tumor cell proliferation (<xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B43">43</xref>). <italic>In vivo</italic>, xenograft assays in mice had verified that stable knockdown of circ_0003945 led to reduced tumor volumes and weights compared matched controls. These findings indicate a promotive role for circ_0003945 in tumorigenesis, underlining its potential significance in cancer progression (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>).</p>
</sec>
<sec id="s2_1_2">
<label>2.1.2</label>
<title>Apoptosis</title>
<p>Apoptosis, an evolutionarily conserved mechanism, plays a critical role in cellular turnover and tissue regeneration. A hallmark of this process is the release of cytochrome c from mitochondria. The regulatory framework of apoptosis involves a self-amplifying cascade among pro-apoptotic and anti-apoptotic proteins of the Bcl-2 family, along with the initiator caspases (caspase-8, -9, and -10) and downstream effector caspases (caspase-3, -6, and -7). In tumor cells, a disruption of this balance often triggers the apoptotic pathway, highlighting its potential as a target in cancer therapies (<xref ref-type="bibr" rid="B78">78</xref>, <xref ref-type="bibr" rid="B79">79</xref>). Knockdown of circ_0003945 increased pro-apoptotic proteins Bax and caspase-3 and decreased anti-apoptotic protein Bcl-2, thereby inducing apoptosis in CC cells. It might exert functions by serving as a ceRNA for miR&#x2212;361&#x2212;3p, hampering SOX4 and thus impeding tumor cell progression (<xref ref-type="bibr" rid="B56">56</xref>). Knockdown of circ_0003945 reduced the expression of Bcl-2, conversely while elevating Bax and caspase-3 in OC cells. And overexpressing miR-382-5p could reverse this impact on apoptosis-related proteins and downstream PRPF8 gene (<xref ref-type="bibr" rid="B68">68</xref>). Furthermore, the study reported that, in NSCLC cell, silencing of circ_0003945 led to the downregulation of apoptosis-associated genes and proteins such as c-IAP1, Bcl-2, Survivin, and cell cycle protein CDK6, cyclin D1 were, while upregulation p27 and Bax (<xref ref-type="bibr" rid="B51">51</xref>). C-MYC is a multifunctional TF often associated with hepatocarcinogenesis. Its overexpression can enhance hepatocyte apoptosis (<xref ref-type="bibr" rid="B80">80</xref>). Previous studies indicated c-MYC as a crucial driver in transforming hepatocytes from the G0/G1 phase to the S phase (<xref ref-type="bibr" rid="B81">81</xref>). Overexpressing circ_0003945 notably increased the expression of c-MYC and cellular DNA synthesis, inhibited apoptosis in HCC. This mechanism accompanied by sponging miR-1294 (<xref ref-type="bibr" rid="B66">66</xref>).</p>
</sec>
<sec id="s2_1_3">
<label>2.1.3</label>
<title>Autophagy</title>
<p>Autophagy is an essential catabolic process that recycles limited intracellular resources and mediates the degradation of damaged or redundant organelles under stress conditions to preserve cellular functionality (<xref ref-type="bibr" rid="B73">73</xref>). Previous studies have shown that epithelial cells can evade anoikis though autophagy and epithelial-mesenchymal transition (EMT), facilitating cell migration and invasion (<xref ref-type="bibr" rid="B82">82</xref>, <xref ref-type="bibr" rid="B83">83</xref>). The accumulation of LC3B-II and the conversion from LC3B-I to LC3B-II is sensitive autophagy induction markers. In CRC, silencing circ_0003945 decreased total autophagosomes and autolysosomes formation. This knockdown impeded the expression of LC3B-II, lowered LC3B-I/II conversion rates, and decreased the degradation of key autophagy-related proteins like Beclin1, ATG7, and FOXO1. It was demonstrated that modulating circ_0003945 affected the miR-582-5p/FOXO1 axis, thereby inducing autophagy and promoting migration and invasion of CRC cells (<xref ref-type="bibr" rid="B40">40</xref>).</p>
</sec>
<sec id="s2_1_4">
<label>2.1.4</label>
<title>Metastasis</title>
<p>The invasion-metastasis cascade, pivotal in cancer progression, involves extracellular matrix (ECM) degradation by a broad extent of cells and matrikines such as MMPs, Versican, and others. MMP-9, in particular, remodels the ECM, influencing tumor invasion, metastasis, and angiogenesis. The alteration of tumor stroma and release of angiogenic factors are key strategies in this process, supported by MMP-mediated vasculature growth (<xref ref-type="bibr" rid="B84">84</xref>&#x2013;<xref ref-type="bibr" rid="B86">86</xref>). EMT is a cellular-transformed process marking by changes from E-cadherin&#x2013;expressing epithelial cells to a mesenchymal phenotype expressing vimentin and N-cadherin, endowing tumor cells to migrate and invade (<xref ref-type="bibr" rid="B83">83</xref>, <xref ref-type="bibr" rid="B87">87</xref>). In HCC cells, downregulating circ_0003945 enhanced E-cadherin and reduced N-cadherin and &#x3b1;-SMA levels, suggesting it EMT and invasion (<xref ref-type="bibr" rid="B52">52</xref>). Overexpression of circ_0003945 in NSCLC cells increased MMP9 and Fibronectin, reduced E-Cadherin via KLF4 and miR-3182, and activated Rac1/FAK1/MMP2 and JNK/MAPK pathways, promoting migration and invasion (<xref ref-type="bibr" rid="B51">51</xref>). In the glioma cell lines, downregulation of circ_0003945 brought on a diminished level of MMP9. But this effect could be reversed by miR-1205 or miR-382 depletion, indicating a regulatory role in cell migration and invasion (<xref ref-type="bibr" rid="B62">62</xref>). Furthermore, circ_0003945 dysregulated the Wnt/&#x3b2;-catenin pathway in HCC cells. It sponged miR-34c-5p to upregulate LGR4, activating &#x3b2;-catenin and accelerating migration. CHIR-9902127, a Wnt/&#x3b2;-catenin activator, showed reduced &#x3b2;-catenin phosphorylation in circ_0003945-knockdown HCC cells (<xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B88">88</xref>). Additionally, sponging with miR-194-3p upregulated MMP9, a &#x3b2;-catenin target, facilitating HCC progression (<xref ref-type="bibr" rid="B42">42</xref>).</p>
</sec>
<sec id="s2_1_5">
<label>2.1.5</label>
<title>Angiogenesis</title>
<p>Tumor cells often secrete high levels of pro-angiogenic factors which contribute to the development of an abnormal vascular network. However, the immaturity of tumor blood vessels impairs their functionality for the tumor microenvironment (TME) and increases risk of metastatic dissemination (<xref ref-type="bibr" rid="B89">89</xref>). Among these factors, VEGF, particularly VEGFA from the VEGF family, plays a pivotal role. VEGFA is crucial for cell proliferation, invasion, and angiogenesis in various malignancies (<xref ref-type="bibr" rid="B90">90</xref>). Circ_0003945 sponged miR-199a to upregulate VEGFA to promote CRC progression. And inhibiting miR-199a or overexpressing VEGFA could reverse the tumor-suppressing effects of circ_0003945 knockdown (<xref ref-type="bibr" rid="B54">54</xref>). Meanwhile, the tube formation assay in glioma cell lines revealed that knockdown of circ_0003945 led to reduced angiogenesis, evidenced by a decrease in branch formation. This suggested that circ_0003945 influenced the angiogenic capacity of glioma cells by the miR-638/SZRD1 axis (<xref ref-type="bibr" rid="B39">39</xref>).</p>
</sec>
<sec id="s2_1_6">
<label>2.1.6</label>
<title>Immune escape</title>
<p>Malignant tumor cells often evade the surveillance of immune system, where immune cells can normally identify and eliminate malignancies. Tumor cells alter their structure, effect genes and protein expression within TME to evade immune surveillance, presenting a significant challenge to immunotherapy (<xref ref-type="bibr" rid="B91">91</xref>, <xref ref-type="bibr" rid="B92">92</xref>). Cancer-associated fibroblasts (CAFs), prevalent in the TME, can contribute to this evasion. They aid tumor progression through ECM remodeling, growth factor production, cytokines and chemokines secretion, and metabolic and angiogenic modulation (<xref ref-type="bibr" rid="B93">93</xref>). In hepatitis virus-induced cirrhosis or liver cancer, CAFs originated from hepatic stellate cells and gradually transformed into a major ECM source due to the stroma cell accumulation. HCC-associated fibroblast implied CAF-derived CXCL11 enhanced cell invasion by regulating the circ_0003945/miR-4756/IFIT1/3 axis. Tumor cell morphology was altered from flattened to spindle-shaped and produced more pseudopods, causing elevated cell proliferation, DNA synthesis, migration ability, and protein levels of migration-related markers vimentin and twist (<xref ref-type="bibr" rid="B67">67</xref>). In pancreatic adenocarcinoma (PAAD), the circ_0003945/miR-494 axis regulated PAAD progression by CXCR4 and ZEB1, key mediators of tumor immune cell infiltration. Elevated CXCR4 and ZEB1 levels associated with immune cell markers and immune checkpoint proteins. This axis promotes M2 macrophage polarization of tumor-associated macrophages (TAMs), Treg recruitment and activation in TME, and induced T-cell depletion for immunological escape (<xref ref-type="bibr" rid="B53">53</xref>).</p>
</sec>
</sec>
<sec id="s2_2">
<label>2.2</label>
<title>The potential molecular mechanisms of circ_0003945 regulating tumorigenesis</title>
<p>CircRNAs exert multiple biological functions, notably though the ceRNA mechanism mentioned upward. Previously described as the &#x201c;Rosetta stone of a hidden RNA language,&#x201d; ceRNA has garnered significant attention and undergone extensive research, bolstered by next-generation sequencing technology (<xref ref-type="bibr" rid="B94">94</xref>). CeRNAs cross regulate each other through sequestration of shared miRNAs and form complex regulatory networks based on their miRNA signature (<xref ref-type="bibr" rid="B95">95</xref>). Advances in sequencing technology have increasingly shown that ncRNAs, such as pseudogenes, small and long ncRNAs, and circRNAs, are key in biological processes and tumorigenesis (<xref ref-type="bibr" rid="B96">96</xref>, <xref ref-type="bibr" rid="B97">97</xref>). MiRNAs are a short, single-stranded, and highly conserved class of 18- to 24-nt endogenous ncRNAs, undergo a multistep biogenesis process. Initiated by RNA pol II, the process produces primary-microRNAs (pri-miRNAs), which are cleaved into precursor-miRNA (pre-miRNA) by the Drosha-DGCR8 complex (<xref ref-type="bibr" rid="B98">98</xref>). Exported to the cytoplasm, these pre-miRNAs are further processed by ribonuclease Dicer into small double-stranded RNA (dsRNA) fragments. The functional strand is incorporated into the Argonaute (AGO) protein, forming the RNA-induced silencing complex (RISC). This complex functions as the primary effector in biological processes (<xref ref-type="bibr" rid="B99">99</xref>, <xref ref-type="bibr" rid="B100">100</xref>). Mature miRNAs bind complementarily to the 3&#x2032;untranslated region (3&#x2032;UTR) of the target mRNA through miRNA response elements, either by base pairing or via additional sequence elements. AGO interacts with the polyA-tailed binding in the 3&#x2032;end of mRNA by recruiting adapter protein TNRC6. This interaction facilitates post-transcriptional mRNA degradation and translation repression (<xref ref-type="bibr" rid="B101">101</xref>&#x2013;<xref ref-type="bibr" rid="B103">103</xref>).</p>
<p>The mechanism of ceRNA involves endogenous transcripts, rich in miRNA-binding sites, that can remarkably dimmish the miRNA-mediated repression of target gene mRNA. CircRNAs, acting as sponges, compete with these miRNAs to sequester them from their original targets (<xref ref-type="bibr" rid="B97">97</xref>, <xref ref-type="bibr" rid="B104">104</xref>&#x2013;<xref ref-type="bibr" rid="B106">106</xref>). This forms a complex ceRNA network, where transcripts compete for miRNA, collaboratively modulating miRNA activity (<xref ref-type="bibr" rid="B107">107</xref>). Circ_0003945 networks link to the function of protein-coding mRNAs and related signaling pathways, demonstrating the extensive influence of these interactions (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>).</p>
<p>Circ_0003945 has been identified as a regulatory RNA, serving as a miRNA sponge. It specifically hampered miR-370-3p, with the inhibition of miR-370-3p reversing the effects of circ_0003945 on proliferation, apoptosis, and invasion in TC cells. Databases indicated the involvement of PI3K/Akt and Wnt pathway in TC regulation, with the PI3K/Akt/mTOR pathway being notably active in various cancers (<xref ref-type="bibr" rid="B63">63</xref>) (<xref ref-type="bibr" rid="B108">108</xref>). In cisplatin (DDP)-resistant triple-negative breast cancer (TNBC) cells, circ_0003945, functioning as a ceRNA for miR-300, upregulated ASF1B, thereby activating the PI3K/AKT/mTOR signaling and facilitating the DDP resistance to TNBC cells (<xref ref-type="bibr" rid="B64">64</xref>). The Hippo signaling is essential for cell growth and regeneration and works by phosphorylating YAP, with YAP1 being a key oncogenic transcriptional co-activator (<xref ref-type="bibr" rid="B109">109</xref>). In osteosarcoma, circ_0003945 targeted miR-641, which bond to YAP1&#x2019;s 3&#x2032;UTR, promoting cell proliferation, invasion, and EMT (<xref ref-type="bibr" rid="B69">69</xref>). Similar effects were observed in pancreatic ductal adenocarcinoma (PDAC), where circ_0003945 enhanced proliferation and migration through interacting with miR-6820-3p and promoting YAP1 expression (<xref ref-type="bibr" rid="B38">38</xref>). Analyses of circ_0003945-medicated ceRNA network in PAAD, via the Gene Expression Omnibus database, highlighted its influence on key pathways (NF-&#x3ba;B, PI3K-Akt, Wnt) and immune cell infiltration through the miR-494 axis and hub genes (CXCR4, HIF1A, ZEB1, and SDC1) (<xref ref-type="bibr" rid="B53">53</xref>). HMG (HMGB, HMGN, and HMGA) proteins are a family of nuclear proteins that bind to DNA, causing structural changes in chromatin (<xref ref-type="bibr" rid="B110">110</xref>). Circ_0003945 fostered aggressive behavior by sponging miR&#x2212;204&#x2212;3p to upregulate HMGA2 (<xref ref-type="bibr" rid="B71">71</xref>) and sponging miR-637 to upregulate HMGB2 (<xref ref-type="bibr" rid="B72">72</xref>) in osteosarcoma cells. And in esophageal squamous cell carcinoma (<xref ref-type="bibr" rid="B50">50</xref>) and OC (<xref ref-type="bibr" rid="B55">55</xref>), it promoted cancer cell behavior via the miR-422a/Rab10 and miR-144/CHD2 axes, respectively. Overall, the circRNA-miRNA-mRNA regulatory network involving circ_0003945 underscores its crucial role in disease mechanisms (<xref ref-type="fig" rid="f4">
<bold>Figure&#xa0;4</bold>
</xref>).</p>
<fig id="f4" position="float">
<label>Figure&#xa0;4</label>
<caption>
<p>Molecular mechanisms of circ_0003945 in different diseases.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fonc-14-1275009-g004.tif"/>
</fig>
</sec>
</sec>
<sec id="s3">
<label>3</label>
<title>The clinical significance and prognostic value of circ_0003945 in tumors</title>
<p>Overexpression of circ_0003945 tended to mean more aggressive clinicopathological parameters and poorer prognosis for tumor patients in major conditions. Its upregulation was more prone to increased therapy resistance through multiple mechanisms.</p>
<sec id="s3_1">
<label>3.1</label>
<title>The clinical parameters of circ_0003945 in tumors</title>
<p>Numerous studies have identified circRNAs as potential diagnostic biomarker in cancers (<xref ref-type="bibr" rid="B12">12</xref>). Specifically, circ_0003945 expression was found to be higher in various cancer tissues compared to paired adjacent noncancerous tissues, though it is notably decreased in gastric cancer and renal cell carcinoma. (<xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref>). High circ_0003945 levels correlated with aggressive clinicopathological characteristics such as invasive histological types, poor differentiation, higher recurrence rates, extensive microvascular invasion, and advanced tumor-node-metastasis (TNM) stages, including larger tumor size, more lymph node and distant metastases (<xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>). Kaplan&#x2013;Meier survival analysis showed that patients with high circ_0003945 levels had shorter overall survival (OS), indicating a poorer prognosis (<xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>). Moreover, higher circ_0003945 expression was linked to reduced recurrence-free survival (RFS) and is an independent predictor of time to recurrence (TTR) in hepatocellular carcinoma. In tamoxifen-resistant patients, elevated circ_0003945 levels were associated with worse distant metastasis-free survival (DMFS) (<xref ref-type="bibr" rid="B65">65</xref>).</p>
<p>Currently, there are no related clinical trials targeting circ_0003945 in human diseases. However, some other clinical trials targeting circRNAs have been carried out so far. For example, studies identified and compared differentially expressed of relevant circRNAs in various cells or tissues. Independent cohorts confirmed the potential of certain circRNAs as sensitive and specific biomarkers for diseases diagnosis and prognosis prediction (<xref ref-type="bibr" rid="B111">111</xref>&#x2013;<xref ref-type="bibr" rid="B114">114</xref>).</p>
</sec>
<sec id="s3_2">
<label>3.2</label>
<title>Circ_0003945-related therapeutic resistance</title>
<p>Cancer therapeutic resistance is broadly classified into intrinsic and acquired (including adaptive) types, with tumor cells traditionally categorized as either drug-sensitive or drug-resistant. Resistance often involves pathway-based mechanisms, with activation of drug-inhibited effector proteins upstream, parallel, or downstream of the primary targets (<xref ref-type="bibr" rid="B115">115</xref>). The upregulation of circ_0003945 has been linked to augmented cisplatin resistance in TNBC cells. Circ_0003945 curbed TNBC sensitivity to cisplatin through the miR-300/ASF1B axis by activating PI3K/AKT/mTOR pathway (<xref ref-type="bibr" rid="B64">64</xref>). Knockdown of circ_0003945 hampered SEMA6D to reversing cisplatin resistance via sponging miR-506-3p by restraining the Wnt/&#x3b2;-catenin signaling pathway in osteosarcoma (<xref ref-type="bibr" rid="B70">70</xref>). Conversely, as a tumor suppressor gene in gastric cancer, circ_0003945 hindered cisplatin resistance through the miR-300/KAT6B axis (<xref ref-type="bibr" rid="B59">59</xref>). Additionally, the depletion of circ_0003496 suppressed tumor growth and enhanced doxorubicin (DXR) sensitivity in osteosarcoma by targeting KLF12 via miR-370 (<xref ref-type="bibr" rid="B37">37</xref>). In NSCLC, its downregulation significantly mitigated resistance to docetaxel, DXR, and gefitinib, via restricting KLF4 through modulation of miR-3182 (<xref ref-type="bibr" rid="B43">43</xref>). Furthermore, research discovered a potential mechanism in tamoxifen resistant, where circ_0003945 acting though miR-1296-5p/STAT1 axis, contributed to tamoxifen-resistant in luminal breast tumors (<xref ref-type="bibr" rid="B65">65</xref>). In glioma cells, inhibiting circ_0003945 increased radiosensitivity by weakening RNF2 and counteracting the effects of miR-433-3p (<xref ref-type="bibr" rid="B61">61</xref>).</p>
<p>Generally, the upregulation of circ_0003945 was consistently associated with therapeutic resistance by signaling pathways in drug-resistant cancer cell lines and tissues (<xref ref-type="bibr" rid="B37">37</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B59">59</xref>, <xref ref-type="bibr" rid="B61">61</xref>, <xref ref-type="bibr" rid="B64">64</xref>, <xref ref-type="bibr" rid="B65">65</xref>, <xref ref-type="bibr" rid="B70">70</xref>). It might provide novel perspective on reserving drug resistance or improving radiosensitivity in tumor therapy.</p>
</sec>
</sec>
<sec id="s4">
<label>4</label>
<title>Role of circ_0003945 in non-malignant conditions</title>
<p>In cardiovascular disease, circ_0003945 was correlated with microcirculatory perfusion. It inhibited the migratory activity and promoted M2 polarization in macrophages, declining the productions of cytokines TNF-&#x3b1;, interleukin (IL)-1&#x3b2;, and MCP-1 and the PI3K/AKT/mTOR pathway.</p>
<p>The expression of circ_0003945 might predict prognosis in extracorporeal membrane oxygenation (ECMO) patients with cardiogenic shock (<xref ref-type="bibr" rid="B45">45</xref>). In a canine ECMO model, the modifications of pulsatility improved microcirculatory perfusion and endothelial integrity. The upregulation of circ_0003945 stabilized endothelial tight junction markers ZO-1 and occluding. It followed by modulating the eNOS activity and inhibiting the NF-&#x3ba;B signaling pathway, pivotal in this protective mechanism (<xref ref-type="bibr" rid="B44">44</xref>).</p>
<p>Furthermore, circ_0003945 was upregulated in DR, when knocked down, it alleviated high glucose-triggered oxidative stress and dysfunction in human retinal microvascular endothelial cells (hRMECs). It might offer a promising therapeutic target through the miR589-5p/EGR1 axis for DR (<xref ref-type="bibr" rid="B35">35</xref>). In OA, exosome-mediated circ_0003945 participated in IL-1&#x3b2;&#x2013;induced chondrocyte damage. It stimulated WNT5B via hindered miR-149-5p, affecting chondrocyte proliferation, apoptosis, migration, invasion, inflammation, and ECM degradation (<xref ref-type="bibr" rid="B46">46</xref>). Circ_0003945 was found to be downregulated in placental tissues from patients with PE compared to healthy controls. Its knockdown impeded trophoblast cell proliferation and migration via miR-1244/FOXM1 axis (<xref ref-type="bibr" rid="B47">47</xref>). Interestingly, circ_0003945 was significantly upregulated in cow mammary gland tissue, influencing milk fat metabolism by sponging miR-331-3p (<xref ref-type="bibr" rid="B48">48</xref>). These studies underscore the potential role of circ_0003945 in various diseases beyond tumors.</p>
</sec>
<sec id="s5" sec-type="conclusions">
<label>5</label>
<title>Conclusions and prospects</title>
<p>CircRNAs have garnered widespread attention in contemporary medical research due to their indispensable roles in human diseases pathogenesis. In this review, we discussed a compendium of studies that document the aberrant expression of circ_0003945 in various human diseases. These studies elucidate the specific cellular and biological functions of this circRNA. In most malignancy cases, circ_0003945 served as an oncogene. It functioned as a miRNA sponge, inhibiting the transcription of miRNAs, and thereby activates downstream effector genes. However, in a minority of malignancies, such as GC and RCC, circ_0003945 acted as a tumor suppressor gene. Research has indicated that circ_0003945 could alter the biological behaviors of tumor cells by modulating signaling pathways such as MAPK, Wnt/&#x3b2;-catenin, PI3K/AKT/mTOR, Rac-FAK1, and others. The expression levels of circ_0003945 were strongly correlated with the clinicopathological features of patients, and survival analyses also provided valuable insights into prognosticating clinical outcomes. Moreover, circ_0003945 affected sensitivity to chemotherapy and radiotherapy through alterations in its molecular mechanisms. This finding indicated that circ_0003945 might serve as a valuable predictive biomarker for clinical management of diseases.</p>
<p>Nonetheless, current research on circ_0003945 remands relatively restricted. The primary issue is the obscurity surrounding the upstream regulatory mechanisms of circ_0003945. Within the TRCirc database, the TF-peak of SE FOXA1 is located squarely in the transcriptional domain of circ_0003945. Further empirical validation is needed to determine whether a specific TF can directly and independently regulate the transcription of circ_0003945, thereby impacting the function of downstream proteins. Additionally, most molecular mechanisms identified for circ_0003945 are limited to the model of ceRNA, leaving other functionalities of circRNAs yet to be elucidated. Moreover, there is an insufficient exploration of the correlations with unmentioned sub-histological even pathological types of tumors in experiments. Furthermore, significant advancements in clinical trials, including consecutive biopsies of tumor tissues and circulating plasma sampling, are essential to definitively ascertain whether circ_0003945 can serve as a reliable clinical diagnostic maker. Finally, when relevant clinical trials concerning circ_0003945 are conducted and yield valid conclusions, the potential of circ_0003945 as a target for clinical therapy is expected to be realized.</p>
</sec>
<sec id="s6" sec-type="author-contributions">
<title>Author contributions</title>
<p>XZ: Writing &#x2013; original draft, Conceptualization, Investigation, Visualization. LM: Writing &#x2013; original draft, Conceptualization, Funding acquisition, Investigation, Writing &#x2013; review &amp; editing. LW: Writing &#x2013; original draft, Conceptualization, Visualization, Writing &#x2013; review &amp; editing. HW: Visualization, Writing &#x2013; original draft, Conceptualization. ZW: Funding acquisition, Project administration, Supervision, Writing &#x2013; review &amp; editing, Conceptualization.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (No.82072591, 81871871 to ZW), Jiangsu Province Capability Improvement Project through Science, Technology and Education; Jiangsu Provincial Medical Key Discipline Cultivation Unit (No. JSDW202235 to ZW), Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province (No. SJCX23_0657 to LM), Bethune Medical Science Research Foundation Project (2022-YJ-085-J-Z-ZZ-006).</p>
</sec>
<sec id="s8" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s9" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="B1">
<label>1</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>C</given-names>
</name>
<name>
<surname>Li</surname> <given-names>M</given-names>
</name>
<name>
<surname>Meng</surname> <given-names>H</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Niu</surname> <given-names>W</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Analysis of status and countermeasures of cancer incidence and mortality in China</article-title>. <source>Sci China Life Sci</source>. (<year>2019</year>) <volume>62</volume>:<page-range>640&#x2013;7</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s11427-018-9461-5</pub-id>
</citation>
</ref>
<ref id="B2">
<label>2</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xia</surname> <given-names>C</given-names>
</name>
<name>
<surname>Dong</surname> <given-names>X</given-names>
</name>
<name>
<surname>Li</surname> <given-names>H</given-names>
</name>
<name>
<surname>Cao</surname> <given-names>M</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>D</given-names>
</name>
<name>
<surname>He</surname> <given-names>S</given-names>
</name>
<etal/>
</person-group>. <article-title>Cancer statistics in China and United States, 2022: profiles, trends, and determinants</article-title>. <source>Chin Med J (Engl)</source>. (<year>2022</year>) <volume>135</volume>:<page-range>584&#x2013;90</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/CM9.0000000000002108</pub-id>
</citation>
</ref>
<ref id="B3">
<label>3</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yin</surname> <given-names>W</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Jiang</surname> <given-names>L</given-names>
</name>
<name>
<surname>James Kang</surname> <given-names>Y</given-names>
</name>
</person-group>. <article-title>Cancer and stem cells</article-title>. <source>Exp Biol Med (Maywood)</source>. (<year>2021</year>) <volume>246</volume>:<page-range>1791&#x2013;801</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1177/15353702211005390</pub-id>
</citation>
</ref>
<ref id="B4">
<label>4</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Deng</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>S</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>D</given-names>
</name>
</person-group>. <article-title>Circulating tumor cell isolation for cancer diagnosis and prognosis</article-title>. <source>eBioMedicine</source>. (<year>2022</year>) <volume>83</volume>:<fpage>104237</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.ebiom.2022.104237</pub-id>
</citation>
</ref>
<ref id="B5">
<label>5</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Siegel</surname> <given-names>RL</given-names>
</name>
<name>
<surname>Miller</surname> <given-names>KD</given-names>
</name>
<name>
<surname>Fuchs</surname> <given-names>HE</given-names>
</name>
<name>
<surname>Jemal</surname> <given-names>A</given-names>
</name>
</person-group>. <article-title>Cancer statistics, 2022</article-title>. <source>CA Cancer J Clin</source>. (<year>2022</year>) <volume>72</volume>:<fpage>7</fpage>&#x2013;<lpage>33</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3322/caac.21708</pub-id>
</citation>
</ref>
<ref id="B6">
<label>6</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>I</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>C-Y</given-names>
</name>
<name>
<surname>Chuang</surname> <given-names>T-J</given-names>
</name>
</person-group>. <article-title>Biogenesis, identification, and function of exonic circular RNAs</article-title>. <source>Wiley Interdiscip Rev RNA</source>. (<year>2015</year>) <volume>6</volume>:<page-range>563&#x2013;79</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/wrna.1294</pub-id>
</citation>
</ref>
<ref id="B7">
<label>7</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sanger</surname> <given-names>HL</given-names>
</name>
<name>
<surname>Klotz</surname> <given-names>G</given-names>
</name>
<name>
<surname>Riesner</surname> <given-names>D</given-names>
</name>
<name>
<surname>Gross</surname> <given-names>HJ</given-names>
</name>
<name>
<surname>Kleinschmidt</surname> <given-names>AK</given-names>
</name>
</person-group>. <article-title>Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures</article-title>. <source>Proc Natl Acad Sci U S A</source>. (<year>1976</year>) <volume>73</volume>:<page-range>3852&#x2013;6</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1073/pnas.73.11.3852</pub-id>
</citation>
</ref>
<ref id="B8">
<label>8</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hsu</surname> <given-names>MT</given-names>
</name>
<name>
<surname>Coca-Prados</surname> <given-names>M</given-names>
</name>
</person-group>. <article-title>Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells</article-title>. <source>Nature</source>. (<year>1979</year>) <volume>280</volume>:<page-range>339&#x2013;40</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/280339a0</pub-id>
</citation>
</ref>
<ref id="B9">
<label>9</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kos</surname> <given-names>A</given-names>
</name>
<name>
<surname>Dijkema</surname> <given-names>R</given-names>
</name>
<name>
<surname>Arnberg</surname> <given-names>AC</given-names>
</name>
<name>
<surname>van der Meide</surname> <given-names>PH</given-names>
</name>
<name>
<surname>Schellekens</surname> <given-names>H</given-names>
</name>
</person-group>. <article-title>The hepatitis delta (delta) virus possesses a circular RNA</article-title>. <source>Nature</source>. (<year>1986</year>) <volume>323</volume>:<page-range>558&#x2013;60</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/323558a0</pub-id>
</citation>
</ref>
<ref id="B10">
<label>10</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Obi</surname> <given-names>P</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>YG</given-names>
</name>
</person-group>. <article-title>The design and synthesis of circular RNAs</article-title>. <source>Methods</source>. (<year>2021</year>) <volume>196</volume>:<fpage>85</fpage>&#x2013;<lpage>103</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.ymeth.2021.02.020</pub-id>
</citation>
</ref>
<ref id="B11">
<label>11</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kristensen</surname> <given-names>LS</given-names>
</name>
<name>
<surname>Andersen</surname> <given-names>MS</given-names>
</name>
<name>
<surname>Stagsted</surname> <given-names>LVW</given-names>
</name>
<name>
<surname>Ebbesen</surname> <given-names>KK</given-names>
</name>
<name>
<surname>Hansen</surname> <given-names>TB</given-names>
</name>
<name>
<surname>Kjems</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>The biogenesis, biology and characterization of circular RNAs</article-title>. <source>Nat Rev Genet</source>. (<year>2019</year>) <volume>20</volume>:<page-range>675&#x2013;91</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41576-019-0158-7</pub-id>
</citation>
</ref>
<ref id="B12">
<label>12</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Su</surname> <given-names>M</given-names>
</name>
<name>
<surname>Xiao</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>J</given-names>
</name>
<name>
<surname>Tang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Tian</surname> <given-names>B</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNAs in Cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers</article-title>. <source>Mol Cancer</source>. (<year>2019</year>) <volume>18</volume>:<fpage>90</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12943-019-1002-6</pub-id>
</citation>
</ref>
<ref id="B13">
<label>13</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Schmidt</surname> <given-names>CA</given-names>
</name>
<name>
<surname>Giusto</surname> <given-names>JD</given-names>
</name>
<name>
<surname>Bao</surname> <given-names>A</given-names>
</name>
<name>
<surname>Hopper</surname> <given-names>AK</given-names>
</name>
<name>
<surname>Matera</surname> <given-names>AG</given-names>
</name>
</person-group>. <article-title>Molecular determinants of metazoan tricRNA biogenesis</article-title>. <source>Nucleic Acids Res</source>. (<year>2019</year>) <volume>47</volume>:<page-range>6452&#x2013;65</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/nar/gkz311</pub-id>
</citation>
</ref>
<ref id="B14">
<label>14</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>L</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>C</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>H</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Liang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>The bioinformatics toolbox for circRNA discovery and analysis</article-title>. <source>Brief Bioinform</source>. (<year>2021</year>) <volume>22</volume>:<page-range>1706&#x2013;28</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/bib/bbaa001</pub-id>
</citation>
</ref>
<ref id="B15">
<label>15</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Greene</surname> <given-names>J</given-names>
</name>
<name>
<surname>Baird</surname> <given-names>A-M</given-names>
</name>
<name>
<surname>Brady</surname> <given-names>L</given-names>
</name>
<name>
<surname>Lim</surname> <given-names>M</given-names>
</name>
<name>
<surname>Gray</surname> <given-names>SG</given-names>
</name>
<name>
<surname>McDermott</surname> <given-names>R</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNAs: biogenesis, function and role in human diseases</article-title>. <source>Front Mol Biosci</source>. (<year>2017</year>) <volume>4</volume>:<elocation-id>38</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmolb.2017.00038</pub-id>
</citation>
</ref>
<ref id="B16">
<label>16</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>He</surname> <given-names>AT</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Li</surname> <given-names>F</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>BB</given-names>
</name>
</person-group>. <article-title>Targeting circular RNAs as a therapeutic approach: current strategies and challenges</article-title>. <source>Signal Transduct Target Ther</source>. (<year>2021</year>) <volume>6</volume>:<fpage>185</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41392-021-00569-5</pub-id>
</citation>
</ref>
<ref id="B17">
<label>17</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhou</surname> <given-names>W-Y</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>Z-R</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>D-S</given-names>
</name>
<name>
<surname>Ju</surname> <given-names>H-Q</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>R-H</given-names>
</name>
</person-group>. <article-title>Circular RNA: metabolism, functions and interactions with proteins</article-title>. <source>Mol Cancer</source>. (<year>2020</year>) <volume>19</volume>:<fpage>172</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12943-020-01286-3</pub-id>
</citation>
</ref>
<ref id="B18">
<label>18</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bachmayr-Heyda</surname> <given-names>A</given-names>
</name>
<name>
<surname>Reiner</surname> <given-names>AT</given-names>
</name>
<name>
<surname>Auer</surname> <given-names>K</given-names>
</name>
<name>
<surname>Sukhbaatar</surname> <given-names>N</given-names>
</name>
<name>
<surname>Aust</surname> <given-names>S</given-names>
</name>
<name>
<surname>Bachleitner-Hofmann</surname> <given-names>T</given-names>
</name>
<etal/>
</person-group>. <article-title>Correlation of circular RNA abundance with proliferation&#x2013;exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues</article-title>. <source>Sci Rep</source>. (<year>2015</year>) <volume>5</volume>:<fpage>8057</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/srep08057</pub-id>
</citation>
</ref>
<ref id="B19">
<label>19</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ashwal-Fluss</surname> <given-names>R</given-names>
</name>
<name>
<surname>Meyer</surname> <given-names>M</given-names>
</name>
<name>
<surname>Pamudurti</surname> <given-names>NR</given-names>
</name>
<name>
<surname>Ivanov</surname> <given-names>A</given-names>
</name>
<name>
<surname>Bartok</surname> <given-names>O</given-names>
</name>
<name>
<surname>Hanan</surname> <given-names>M</given-names>
</name>
<etal/>
</person-group>. <article-title>circRNA biogenesis competes with pre-mRNA splicing</article-title>. <source>Mol Cell</source>. (<year>2014</year>) <volume>56</volume>:<fpage>55</fpage>&#x2013;<lpage>66</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.molcel.2014.08.019</pub-id>
</citation>
</ref>
<ref id="B20">
<label>20</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cheng</surname> <given-names>D</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Dong</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X</given-names>
</name>
</person-group>. <article-title>Cancer-related circular RNA: diverse biological functions</article-title>. <source>Cancer Cell Int</source>. (<year>2021</year>) <volume>21</volume>:<fpage>11</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12935-020-01703-z</pub-id>
</citation>
</ref>
<ref id="B21">
<label>21</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>X</given-names>
</name>
<name>
<surname>Li</surname> <given-names>H</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Cheng</surname> <given-names>L</given-names>
</name>
</person-group>. <article-title>Circular RNAs in human cancer</article-title>. <source>Front Oncol</source>. (<year>2020</year>) <volume>10</volume>:<elocation-id>577118</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fonc.2020.577118</pub-id>
</citation>
</ref>
<ref id="B22">
<label>22</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>X</given-names>
</name>
<name>
<surname>Li</surname> <given-names>H</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Cheng</surname> <given-names>L</given-names>
</name>
</person-group>. <article-title>Regulatory effects of circular RNAs on host genes in human cancer</article-title>. <source>Front Oncol</source>. (<year>2020</year>) <volume>10</volume>:<elocation-id>586163</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fonc.2020.586163</pub-id>
</citation>
</ref>
<ref id="B23">
<label>23</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>D</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>A</given-names>
</name>
</person-group>. <article-title>The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function</article-title>. <source>J Neurosci Res</source>. (<year>2020</year>) <volume>98</volume>:<fpage>87</fpage>&#x2013;<lpage>97</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/jnr.24356</pub-id>
</citation>
</ref>
<ref id="B24">
<label>24</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yuan</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>X</given-names>
</name>
<name>
<surname>Du</surname> <given-names>K</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>X</given-names>
</name>
<name>
<surname>Chang</surname> <given-names>S</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer</article-title>. <source>Cell Death Dis</source>. (<year>2022</year>) <volume>13</volume>:<fpage>827</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41419-022-05254-1</pub-id>
</citation>
</ref>
<ref id="B25">
<label>25</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Prats</surname> <given-names>A-C</given-names>
</name>
<name>
<surname>David</surname> <given-names>F</given-names>
</name>
<name>
<surname>Diallo</surname> <given-names>LH</given-names>
</name>
<name>
<surname>Roussel</surname> <given-names>E</given-names>
</name>
<name>
<surname>Tatin</surname> <given-names>F</given-names>
</name>
<name>
<surname>Garmy-Susini</surname> <given-names>B</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNA, the key for translation</article-title>. <source>Int J Mol Sci</source>. (<year>2020</year>) <volume>21</volume>:<fpage>8591</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/ijms21228591</pub-id>
</citation>
</ref>
<ref id="B26">
<label>26</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Shi</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>X</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>The new function of circRNA: translation</article-title>. <source>Clin Transl Oncol</source>. (<year>2020</year>) <volume>22</volume>:<page-range>2162&#x2013;9</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s12094-020-02371-1</pub-id>
</citation>
</ref>
<ref id="B27">
<label>27</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lei</surname> <given-names>M</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>G</given-names>
</name>
<name>
<surname>Ning</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>J</given-names>
</name>
<name>
<surname>Dong</surname> <given-names>D</given-names>
</name>
</person-group>. <article-title>Translation and functional roles of circular RNAs in human cancer</article-title>. <source>Mol Cancer</source>. (<year>2020</year>) <volume>19</volume>:<fpage>30</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12943-020-1135-7</pub-id>
</citation>
</ref>
<ref id="B28">
<label>28</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tao</surname> <given-names>M</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>M</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>S</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>W</given-names>
</name>
<name>
<surname>Ju</surname> <given-names>S</given-names>
</name>
</person-group>. <article-title>CircRNAs and their regulatory roles in cancers</article-title>. <source>Mol Med</source>. (<year>2021</year>) <volume>27</volume>:<fpage>94</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s10020-021-00359-3</pub-id>
</citation>
</ref>
<ref id="B29">
<label>29</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Shang</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>R</given-names>
</name>
<name>
<surname>Ge</surname> <given-names>S</given-names>
</name>
</person-group>. <article-title>The novel roles of circRNAs in human cancer</article-title>. <source>Mol Cancer</source>. (<year>2019</year>) <volume>18</volume>:<fpage>6</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12943-018-0934-6</pub-id>
</citation>
</ref>
<ref id="B30">
<label>30</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Guarnerio</surname> <given-names>J</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Cheloni</surname> <given-names>G</given-names>
</name>
<name>
<surname>Panella</surname> <given-names>R</given-names>
</name>
<name>
<surname>Mae Katon</surname> <given-names>J</given-names>
</name>
<name>
<surname>Simpson</surname> <given-names>M</given-names>
</name>
<etal/>
</person-group>. <article-title>Intragenic antagonistic roles of protein and circRNA in tumorigenesis</article-title>. <source>Cell Res</source>. (<year>2019</year>) <volume>29</volume>:<page-range>628&#x2013;40</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41422-019-0192-1</pub-id>
</citation>
</ref>
<ref id="B31">
<label>31</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tang</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>J</given-names>
</name>
<name>
<surname>Qian</surname> <given-names>F</given-names>
</name>
<name>
<surname>Feng</surname> <given-names>C</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>TRCirc: a resource for transcriptional regulation information of circRNAs</article-title>. <source>Brief Bioinform</source>. (<year>2019</year>) <volume>20</volume>:<page-range>2327&#x2013;33</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/bib/bby083</pub-id>
</citation>
</ref>
<ref id="B32">
<label>32</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zlotorynski</surname> <given-names>E</given-names>
</name>
</person-group>. <article-title>Non-coding RNA: Circular RNAs promote transcription</article-title>. <source>Nat Rev Mol Cell Biol</source>. (<year>2015</year>) <volume>16</volume>:<fpage>206</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/nrm3967</pub-id>
</citation>
</ref>
<ref id="B33">
<label>33</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>X-C</given-names>
</name>
<name>
<surname>Tang</surname> <given-names>Z-D</given-names>
</name>
<name>
<surname>Peng</surname> <given-names>L</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y-Y</given-names>
</name>
<name>
<surname>Qian</surname> <given-names>F-C</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>J-M</given-names>
</name>
<etal/>
</person-group>. <article-title>Integrative epigenomic analysis of transcriptional regulation of human circRNAs</article-title>. <source>Front Genet</source>. (<year>2020</year>) <volume>11</volume>:<elocation-id>590672</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fgene.2020.590672</pub-id>
</citation>
</ref>
<ref id="B34">
<label>34</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>S</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>R</given-names>
</name>
<name>
<surname>Kang</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Upregulation of circ-UBAP2 predicts poor prognosis and promotes triple-negative breast cancer progression through the miR-661/MTA1 pathway</article-title>. <source>Biochem Biophys Res Commun</source>. (<year>2018</year>) <volume>505</volume>:<fpage>996</fpage>&#x2013;<lpage>1002</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.bbrc.2018.10.026</pub-id>
</citation>
</ref>
<ref id="B35">
<label>35</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jiewei</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Jingjing</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Jingjing</surname> <given-names>X</given-names>
</name>
<name>
<surname>Guilan</surname> <given-names>Z</given-names>
</name>
</person-group>. <article-title>Downregulation of circ-UBAP2 ameliorates oxidative stress and dysfunctions of human retinal microvascular endothelial cells (hRMECs) via miR-589-5p/EGR1 axis</article-title>. <source>Bioengineered</source>. (<year>2021</year>) <volume>12</volume>:<page-range>7508&#x2013;18</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/21655979.2021.1979440</pub-id>
</citation>
</ref>
<ref id="B36">
<label>36</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xiong</surname> <given-names>H</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>G</given-names>
</name>
<name>
<surname>Su</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Q</given-names>
</name>
<etal/>
</person-group>. <article-title>Emerging roles of circUBAP2 targeting miR-370-3p in proliferation, apoptosis, and invasion of papillary thyroid cancer cells</article-title>. <source>Hum Cell</source>. (<year>2021</year>) <volume>34</volume>:<page-range>1866&#x2013;77</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s13577-021-00585-1</pub-id>
</citation>
</ref>
<ref id="B37">
<label>37</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xie</surname> <given-names>C</given-names>
</name>
<name>
<surname>Liang</surname> <given-names>G</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Lin</surname> <given-names>E</given-names>
</name>
</person-group>. <article-title>Circular RNA hsa_circ_0003496 Contributes to Tumorigenesis and Chemoresistance in Osteosarcoma Through Targeting (microRNA) miR-370/Kr&#xfc;ppel-Like Factor 12 Axis</article-title>. <source>Cancer Manag Res</source>. (<year>2020</year>) <volume>12</volume>:<page-range>8229&#x2013;40</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.2147/CMAR.S253969</pub-id>
</citation>
</ref>
<ref id="B38">
<label>38</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhang</surname> <given-names>H</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>X</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>L</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X</given-names>
</name>
<name>
<surname>Feng</surname> <given-names>D</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>M</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression</article-title>. <source>Cell Death Dis</source>. (<year>2022</year>) <volume>13</volume>:<fpage>736</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41419-022-05188-8</pub-id>
</citation>
</ref>
<ref id="B39">
<label>39</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Deng</surname> <given-names>L</given-names>
</name>
<name>
<surname>Gong</surname> <given-names>K</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>G</given-names>
</name>
</person-group>. <article-title>Hsa_circ_0008344 promotes glioma tumor progression and angiogenesis presumably by regulating miR-638/SZRD1 pathway</article-title>. <source>Neurotox Res</source>. (<year>2022</year>) <volume>40</volume>:<page-range>825&#x2013;36</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s12640-022-00504-8</pub-id>
</citation>
</ref>
<ref id="B40">
<label>40</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chen</surname> <given-names>F</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>L</given-names>
</name>
<name>
<surname>Di</surname> <given-names>J</given-names>
</name>
<name>
<surname>Li</surname> <given-names>M</given-names>
</name>
<name>
<surname>Dong</surname> <given-names>D</given-names>
</name>
<name>
<surname>Pei</surname> <given-names>D</given-names>
</name>
</person-group>. <article-title>Circular RNA ubiquitin-associated protein 2 enhances autophagy and promotes colorectal cancer progression and metastasis via miR-582-5p/FOXO1 signaling</article-title>. <source>J Genet Genomics</source>. (<year>2021</year>) <volume>48</volume>:<page-range>1091&#x2013;103</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.jgg.2021.07.017</pub-id>
</citation>
</ref>
<ref id="B41">
<label>41</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Lyu</surname> <given-names>L-H</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>C-Y</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>W-J</given-names>
</name>
<name>
<surname>Jin</surname> <given-names>A-L</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>H</given-names>
</name>
<etal/>
</person-group>. <article-title>Hsa_circ_0003945 promotes progression of hepatocellular carcinoma by mediating miR-34c-5p/LGR4/&#x3b2;-catenin axis activity</article-title>. <source>J Cell Mol Med</source>. (<year>2022</year>) <volume>26</volume>:<page-range>2218&#x2013;29</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/jcmm.17243</pub-id>
</citation>
</ref>
<ref id="B42">
<label>42</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>B</given-names>
</name>
<name>
<surname>Tian</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>M</given-names>
</name>
<name>
<surname>Shen</surname> <given-names>H</given-names>
</name>
<name>
<surname>Xia</surname> <given-names>J</given-names>
</name>
<name>
<surname>Nan</surname> <given-names>J</given-names>
</name>
<etal/>
</person-group>. <article-title>CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma</article-title>. <source>Front Cell Dev Biol</source>. (<year>2021</year>) <volume>9</volume>:<elocation-id>675043</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fcell.2021.675043</pub-id>
</citation>
</ref>
<ref id="B43">
<label>43</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zheng</surname> <given-names>G</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>W</given-names>
</name>
<name>
<surname>You</surname> <given-names>P</given-names>
</name>
<name>
<surname>Ding</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Tu</surname> <given-names>P</given-names>
</name>
</person-group>. <article-title>circUBAP2 exacerbates Malignant capabilities of NSCLC by targeting KLF4 through miR-3182 modulation</article-title>. <source>Aging (Albany NY)</source>. (<year>2021</year>) <volume>13</volume>:<page-range>11083&#x2013;95</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.18632/aging.v13i8</pub-id>
</citation>
</ref>
<ref id="B44">
<label>44</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>G</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>S</given-names>
</name>
<name>
<surname>Zeng</surname> <given-names>J</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Meng</surname> <given-names>F</given-names>
</name>
<name>
<surname>Tang</surname> <given-names>Z</given-names>
</name>
<etal/>
</person-group>. <article-title>Arterial Pulsatility Augments Microcirculatory Perfusion and Maintains the Endothelial Integrity during Extracorporeal Membrane Oxygenation via hsa_circ_0007367 Upregulation in a Canine Model with Cardiac Arrest</article-title>. <source>Oxid Med Cell Longev</source>. (<year>2022</year>) <volume>2022</volume>:<fpage>1630918</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1155/2022/1630918</pub-id>
</citation>
</ref>
<ref id="B45">
<label>45</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>J</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Zeng</surname> <given-names>J</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNA UBAP2 (hsa_circ_0007367) correlates with microcirculatory perfusion and predicts outcomes of cardiogenic shock patients undergoing extracorporeal membrane oxygenation support</article-title>. <source>Shock</source>. (<year>2022</year>) <volume>57</volume>:<page-range>200&#x2013;10</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/SHK.0000000000001937</pub-id>
</citation>
</ref>
<ref id="B46">
<label>46</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhu</surname> <given-names>C</given-names>
</name>
<name>
<surname>Shen</surname> <given-names>K</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>W</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>H</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>Y</given-names>
</name>
</person-group>. <article-title>Exosome-mediated circ_0001846 participates in IL-1&#x3b2;-induced chondrocyte cell damage by miR-149-5p-dependent regulation of WNT5B</article-title>. <source>Clin Immunol</source>. (<year>2021</year>) <volume>232</volume>:<fpage>108856</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.clim.2021.108856</pub-id>
</citation>
</ref>
<ref id="B47">
<label>47</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Qi</surname> <given-names>T</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>D</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>X</given-names>
</name>
<name>
<surname>Li</surname> <given-names>M</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>H</given-names>
</name>
</person-group>. <article-title>Decreased circUBAP2 expression is associated with preeclampsia by limiting trophoblast cell proliferation and migration</article-title>. <source>Reprod Sci</source>. (<year>2021</year>) <volume>28</volume>:<page-range>2237&#x2013;45</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s43032-020-00450-w</pub-id>
</citation>
</ref>
<ref id="B48">
<label>48</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Feng</surname> <given-names>X</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Mu</surname> <given-names>T</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>B</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>R</given-names>
</name>
<etal/>
</person-group>. <article-title>CircRNA screening and ceRNA network construction for milk fat metabolism in dairy cows</article-title>. <source>Front Vet Sci</source>. (<year>2022</year>) <volume>9</volume>:<elocation-id>995629</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fvets.2022.995629</pub-id>
</citation>
</ref>
<ref id="B49">
<label>49</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhou</surname> <given-names>J</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>H</given-names>
</name>
<name>
<surname>Chu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Li</surname> <given-names>G</given-names>
</name>
<name>
<surname>Yan</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNA hsa_circ_0008344 regulates glioblastoma cell proliferation, migration, invasion, and apoptosis</article-title>. <source>J Clin Lab Anal</source>. (<year>2018</year>) <volume>32</volume>:<fpage>e22454</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/jcla.22454</pub-id>
</citation>
</ref>
<ref id="B50">
<label>50</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Zhi</surname> <given-names>L</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>L</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>F</given-names>
</name>
</person-group>. <article-title>Knockdown of circular RNA UBAP2 inhibits the Malignant behaviours of esophageal squamous cell carcinoma by microRNA-422a/Rab10 axis</article-title>. <source>Clin Exp Pharmacol Physiol</source>. (<year>2020</year>) <volume>47</volume>:<page-range>1283&#x2013;90</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/1440-1681.13269</pub-id>
</citation>
</ref>
<ref id="B51">
<label>51</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yin</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>H</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>J</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>Y</given-names>
</name>
</person-group>. <article-title>[Effect of circular RNA UBAP2 silencing on proliferation and invasion of human lung cancer A549 cells and its mechanism]</article-title>. <source>Zhongguo Fei Ai Za Zhi</source>. (<year>2017</year>) <volume>20</volume>:<page-range>800&#x2013;7</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.3779/j.issn.1009-3419.2017.12.02</pub-id>
</citation>
</ref>
<ref id="B52">
<label>52</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>R</given-names>
</name>
<name>
<surname>Li</surname> <given-names>J</given-names>
</name>
<name>
<surname>Tang</surname> <given-names>S</given-names>
</name>
<name>
<surname>Li</surname> <given-names>S</given-names>
</name>
<name>
<surname>Tong</surname> <given-names>Q</given-names>
</name>
<etal/>
</person-group>. <article-title>Circular RNA hsa_circ_0003141 promotes tumorigenesis of hepatocellular carcinoma via a miR-1827/UBAP2 axis</article-title>. <source>Aging (Albany NY)</source>. (<year>2020</year>) <volume>12</volume>:<page-range>9793&#x2013;806</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.18632/aging.v12i10</pub-id>
</citation>
</ref>
<ref id="B53">
<label>53</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhao</surname> <given-names>R</given-names>
</name>
<name>
<surname>Ni</surname> <given-names>J</given-names>
</name>
<name>
<surname>Lu</surname> <given-names>S</given-names>
</name>
<name>
<surname>Jiang</surname> <given-names>S</given-names>
</name>
<name>
<surname>You</surname> <given-names>L</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>H</given-names>
</name>
<etal/>
</person-group>. <article-title>CircUBAP2-mediated competing endogenous RNA network modulates tumorigenesis in pancreatic adenocarcinoma</article-title>. <source>Aging (Albany NY)</source>. (<year>2019</year>) <volume>11</volume>:<page-range>8484&#x2013;501</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.18632/aging.v11i19</pub-id>
</citation>
</ref>
<ref id="B54">
<label>54</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Dai</surname> <given-names>J</given-names>
</name>
<name>
<surname>Zhuang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Tang</surname> <given-names>M</given-names>
</name>
<name>
<surname>Qian</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>J-P</given-names>
</name>
</person-group>. <article-title>CircRNA UBAP2 facilitates the progression of colorectal cancer by regulating miR-199a/VEGFA pathway</article-title>. <source>Eur Rev Med Pharmacol Sci</source>. (<year>2020</year>) <volume>24</volume>:<page-range>7963&#x2013;71</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.26355/eurrev_202008_22479</pub-id>
</citation>
</ref>
<ref id="B55">
<label>55</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sheng</surname> <given-names>M</given-names>
</name>
<name>
<surname>Wei</surname> <given-names>N</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>H-Y</given-names>
</name>
<name>
<surname>Yan</surname> <given-names>M</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>Q-X</given-names>
</name>
<name>
<surname>Jing</surname> <given-names>L-J</given-names>
</name>
</person-group>. <article-title>CircRNA UBAP2 promotes the progression of ovarian cancer by sponging microRNA-144</article-title>. <source>Eur Rev Med Pharmacol Sci</source>. (<year>2019</year>) <volume>23</volume>:<page-range>7283&#x2013;94</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.26355/eurrev_201909_18833</pub-id>
</citation>
</ref>
<ref id="B56">
<label>56</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Meng</surname> <given-names>L</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>X</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>W</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>C</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>J</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>F</given-names>
</name>
</person-group>. <article-title>Circular RNA UBAP2 contributes to tumor growth and metastasis of cervical cancer via modulating miR-361-3p/SOX4 axis</article-title>. <source>Cancer Cell Int</source>. (<year>2020</year>) <volume>20</volume>:<fpage>357</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12935-020-01436-z</pub-id>
</citation>
</ref>
<ref id="B57">
<label>57</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Li</surname> <given-names>X</given-names>
</name>
<name>
<surname>Azhati</surname> <given-names>B</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>W</given-names>
</name>
<name>
<surname>Rexiati</surname> <given-names>M</given-names>
</name>
<name>
<surname>Xing</surname> <given-names>C</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
</person-group>. <article-title>Circular RNA UBAP2 promotes the proliferation of prostate cancer cells via the miR-1244/MAP3K2 axis</article-title>. <source>Oncol Lett</source>. (<year>2021</year>) <volume>21</volume>:<fpage>486</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3892/ol</pub-id>
</citation>
</ref>
<ref id="B58">
<label>58</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhang</surname> <given-names>H</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>G</given-names>
</name>
<name>
<surname>Ding</surname> <given-names>C</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>P</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>R</given-names>
</name>
<name>
<surname>Ding</surname> <given-names>W</given-names>
</name>
<etal/>
</person-group>. <article-title>Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression</article-title>. <source>Oncotarget</source>. (<year>2017</year>) <volume>8</volume>:<page-range>61687&#x2013;97</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.18632/oncotarget.v8i37</pub-id>
</citation>
</ref>
<ref id="B59">
<label>59</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Cheng</surname> <given-names>W</given-names>
</name>
<name>
<surname>Luan</surname> <given-names>P</given-names>
</name>
<name>
<surname>Jin</surname> <given-names>X</given-names>
</name>
</person-group>. <article-title>circUBAP2 inhibits cisplatin resistance in gastric cancer via miR-300/KAT6B axis</article-title>. <source>Anticancer Drugs</source>. (<year>2023</year>) <volume>34</volume>:<page-range>126&#x2013;34</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1097/CAD.0000000000001391</pub-id>
</citation>
</ref>
<ref id="B60">
<label>60</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sun</surname> <given-names>J</given-names>
</name>
<name>
<surname>Yin</surname> <given-names>A</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>W</given-names>
</name>
<name>
<surname>Lv</surname> <given-names>J</given-names>
</name>
<name>
<surname>Liang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Li</surname> <given-names>H</given-names>
</name>
<etal/>
</person-group>. <article-title>CircUBAP2 Inhibits Proliferation and Metastasis of Clear Cell Renal Cell Carcinoma via Targeting miR-148a-3p/FOXK2 Pathway</article-title>. <source>Cell Transplant</source>. (<year>2020</year>) <volume>29</volume>:<fpage>963689720925751</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1177/0963689720925751</pub-id>
</citation>
</ref>
<ref id="B61">
<label>61</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Di</surname> <given-names>L</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>X</given-names>
</name>
<name>
<surname>Ding</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Knockdown of circ_0008344 contributes to radiosensitization in glioma via miR-433-3p/RNF2 axis</article-title>. <source>J Biosci</source>. (<year>2021</year>) <volume>46</volume>:<fpage>82</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s12038-021-00198-8</pub-id>
</citation>
</ref>
<ref id="B62">
<label>62</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Li</surname> <given-names>T</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>B</given-names>
</name>
</person-group>. <article-title>Circ-UBAP2 functions as sponges of miR-1205 and miR-382 to promote glioma progression by modulating STC1 expression</article-title>. <source>Cancer Med</source>. (<year>2021</year>) <volume>10</volume>:<page-range>1815&#x2013;28</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/cam4.3759</pub-id>
</citation>
</ref>
<ref id="B63">
<label>63</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xiong</surname> <given-names>H</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>G</given-names>
</name>
<name>
<surname>Su</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Q</given-names>
</name>
<etal/>
</person-group>. <article-title>Emerging roles of circUBAP2 targeting miR-370-3p in proliferation, apoptosis, and invasion of papillary thyroid cancer cells</article-title>. <source>Hum Cell</source>. (<year>2021</year>) <volume>34</volume>:<page-range>1866&#x2013;77</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s13577-021-00585-1</pub-id>
</citation>
</ref>
<ref id="B64">
<label>64</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>L</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>X</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>F</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>X</given-names>
</name>
<name>
<surname>Li</surname> <given-names>S</given-names>
</name>
</person-group>. <article-title>Circular RNA UBAP2 facilitates the cisplatin resistance of triple-negative breast cancer via microRNA-300/anti-silencing function 1B histone chaperone/PI3K/AKT/mTOR axis</article-title>. <source>Bioengineered</source>. (<year>2022</year>) <volume>13</volume>:<page-range>7197&#x2013;208</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/21655979.2022.2036894</pub-id>
</citation>
</ref>
<ref id="B65">
<label>65</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Huang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Qian</surname> <given-names>M</given-names>
</name>
<name>
<surname>Chu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>L</given-names>
</name>
<name>
<surname>Jian</surname> <given-names>W</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>G</given-names>
</name>
</person-group>. <article-title>Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets</article-title>. <source>Front Mol Biosci</source>. (<year>2023</year>) <volume>10</volume>:<elocation-id>1162259</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fmolb.2023.1162259</pub-id>
</citation>
</ref>
<ref id="B66">
<label>66</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yu</surname> <given-names>M-C</given-names>
</name>
<name>
<surname>Ding</surname> <given-names>G-Y</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>P</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Y-D</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>X-D</given-names>
</name>
<name>
<surname>Cai</surname> <given-names>J-B</given-names>
</name>
<etal/>
</person-group>. <article-title>CircRNA UBAP2 serves as a sponge of miR-1294 to increase tumorigenesis in hepatocellular carcinoma through regulating c-Myc expression</article-title>. <source>Carcinogenesis</source>. (<year>2021</year>) <volume>42</volume>:<page-range>1293&#x2013;303</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1093/carcin/bgab068</pub-id>
</citation>
</ref>
<ref id="B67">
<label>67</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>G</given-names>
</name>
<name>
<surname>Sun</surname> <given-names>J</given-names>
</name>
<name>
<surname>Yang</surname> <given-names>Z-F</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>C</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>P-Y</given-names>
</name>
<name>
<surname>Guan</surname> <given-names>R-Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis</article-title>. <source>Cell Death Dis</source>. (<year>2021</year>) <volume>12</volume>:<fpage>260</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41419-021-03545-7</pub-id>
</citation>
</ref>
<ref id="B68">
<label>68</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xu</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Deng</surname> <given-names>B</given-names>
</name>
<name>
<surname>Li</surname> <given-names>M</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Zhuan</surname> <given-names>L</given-names>
</name>
</person-group>. <article-title>circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis</article-title>. <source>J Ovarian Res</source>. (<year>2020</year>) <volume>13</volume>:<fpage>81</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s13048-020-00685-w</pub-id>
</citation>
</ref>
<ref id="B69">
<label>69</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>H</given-names>
</name>
<name>
<surname>Li</surname> <given-names>W</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>S</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>D</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>M</given-names>
</name>
</person-group>. <article-title>Circular RNA circUBAP2 regulates proliferation and invasion of osteosarcoma cells through miR-641/YAP1 axis</article-title>. <source>Cancer Cell Int</source>. (<year>2020</year>) <volume>20</volume>:<fpage>223</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12935-020-01318-4</pub-id>
</citation>
</ref>
<ref id="B70">
<label>70</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Dong</surname> <given-names>L</given-names>
</name>
<name>
<surname>Qu</surname> <given-names>F</given-names>
</name>
</person-group>. <article-title>CircUBAP2 promotes SEMA6D expression to enhance the cisplatin resistance in osteosarcoma through sponging miR-506-3p by activating Wnt/&#x3b2;-catenin signaling pathway</article-title>. <source>J Mol Histol</source>. (<year>2020</year>) <volume>51</volume>:<page-range>329&#x2013;40</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s10735-020-09883-8</pub-id>
</citation>
</ref>
<ref id="B71">
<label>71</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ma</surname> <given-names>W</given-names>
</name>
<name>
<surname>Xue</surname> <given-names>N</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>D</given-names>
</name>
<name>
<surname>Yao</surname> <given-names>X</given-names>
</name>
<name>
<surname>Lin</surname> <given-names>L</given-names>
</name>
<etal/>
</person-group>. <article-title>circUBAP2 regulates osteosarcoma progression via the miR&#x2212;204&#x2212;3p/HMGA2 axis</article-title>. <source>Int J Oncol</source>. (<year>2021</year>) <volume>58</volume>:<fpage>298</fpage>&#x2013;<lpage>311</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3892/ijo</pub-id>
</citation>
</ref>
<ref id="B72">
<label>72</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ma</surname> <given-names>W</given-names>
</name>
<name>
<surname>Zhao</surname> <given-names>X</given-names>
</name>
<name>
<surname>Gao</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Yao</surname> <given-names>X</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>Q</given-names>
</name>
</person-group>. <article-title>Circular RNA circ_UBAP2 facilitates the progression of osteosarcoma by regulating microRNA miR-637/high-mobility group box (HMGB) 2 axis</article-title>. <source>Bioengineered</source>. (<year>2022</year>) <volume>13</volume>:<page-range>4411&#x2013;27</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/21655979.2022.2033447</pub-id>
</citation>
</ref>
<ref id="B73">
<label>73</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Thompson</surname> <given-names>CB</given-names>
</name>
</person-group>. <article-title>Metabolic regulation of cell growth and proliferation</article-title>. <source>Nat Rev Mol Cell Biol</source>. (<year>2019</year>) <volume>20</volume>:<page-range>436&#x2013;50</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41580-019-0123-5</pub-id>
</citation>
</ref>
<ref id="B74">
<label>74</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Dhillon</surname> <given-names>AS</given-names>
</name>
<name>
<surname>Hagan</surname> <given-names>S</given-names>
</name>
<name>
<surname>Rath</surname> <given-names>O</given-names>
</name>
<name>
<surname>Kolch</surname> <given-names>W</given-names>
</name>
</person-group>. <article-title>MAP kinase signalling pathways in cancer</article-title>. <source>Oncogene</source>. (<year>2007</year>) <volume>26</volume>:<page-range>3279&#x2013;90</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/sj.onc.1210421</pub-id>
</citation>
</ref>
<ref id="B75">
<label>75</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Peng</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Wei</surname> <given-names>W</given-names>
</name>
</person-group>. <article-title>Cell cycle on the crossroad of tumorigenesis and cancer therapy</article-title>. <source>Trends Cell Biol</source>. (<year>2022</year>) <volume>32</volume>:<fpage>30</fpage>&#x2013;<lpage>44</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.tcb.2021.07.001</pub-id>
</citation>
</ref>
<ref id="B76">
<label>76</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yerushalmi</surname> <given-names>R</given-names>
</name>
<name>
<surname>Woods</surname> <given-names>R</given-names>
</name>
<name>
<surname>Ravdin</surname> <given-names>PM</given-names>
</name>
<name>
<surname>Hayes</surname> <given-names>MM</given-names>
</name>
<name>
<surname>Gelmon</surname> <given-names>KA</given-names>
</name>
</person-group>. <article-title>Ki67 in breast cancer: prognostic and predictive potential</article-title>. <source>Lancet Oncol</source>. (<year>2010</year>) <volume>11</volume>:<page-range>174&#x2013;83</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/S1470-2045(09)70262-1</pub-id>
</citation>
</ref>
<ref id="B77">
<label>77</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Andr&#xe9;s-S&#xe1;nchez</surname> <given-names>N</given-names>
</name>
<name>
<surname>Fisher</surname> <given-names>D</given-names>
</name>
<name>
<surname>Krasinska</surname> <given-names>L</given-names>
</name>
</person-group>. <article-title>Physiological functions and roles in cancer of the proliferation marker Ki-67</article-title>. <source>J Cell Sci</source>. (<year>2022</year>) <volume>135</volume>:<fpage>jcs258932</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1242/jcs.258932</pub-id>
</citation>
</ref>
<ref id="B78">
<label>78</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tower</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>Programmed cell death in aging</article-title>. <source>Ageing Res Rev</source>. (<year>2015</year>) <volume>23 Pt A</volume>:<fpage>90</fpage>&#x2013;<lpage>100</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.arr.2015.04.002</pub-id>
</citation>
</ref>
<ref id="B79">
<label>79</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bertheloot</surname> <given-names>D</given-names>
</name>
<name>
<surname>Latz</surname> <given-names>E</given-names>
</name>
<name>
<surname>Franklin</surname> <given-names>BS</given-names>
</name>
</person-group>. <article-title>Necroptosis, pyroptosis and apoptosis: an intricate game of cell death</article-title>. <source>Cell Mol Immunol</source>. (<year>2021</year>) <volume>18</volume>:<page-range>1106&#x2013;21</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41423-020-00630-3</pub-id>
</citation>
</ref>
<ref id="B80">
<label>80</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname> <given-names>H</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>S</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Jia</surname> <given-names>J</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>X</given-names>
</name>
<etal/>
</person-group>. <article-title>TAZ is indispensable for c-MYC-induced hepatocarcinogenesis</article-title>. <source>J Hepatol</source>. (<year>2022</year>) <volume>76</volume>:<page-range>123&#x2013;34</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.jhep.2021.08.021</pub-id>
</citation>
</ref>
<ref id="B81">
<label>81</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Thompson</surname> <given-names>NL</given-names>
</name>
<name>
<surname>Mead</surname> <given-names>JE</given-names>
</name>
<name>
<surname>Braun</surname> <given-names>L</given-names>
</name>
<name>
<surname>Goyette</surname> <given-names>M</given-names>
</name>
<name>
<surname>Shank</surname> <given-names>PR</given-names>
</name>
<name>
<surname>Fausto</surname> <given-names>N</given-names>
</name>
</person-group>. <article-title>Sequential protooncogene expression during rat liver regeneration</article-title>. <source>Cancer Res</source>. (<year>1986</year>) <volume>46</volume>:<page-range>3111&#x2013;7</page-range>.</citation>
</ref>
<ref id="B82">
<label>82</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ashrafizadeh</surname> <given-names>M</given-names>
</name>
<name>
<surname>Mohammadinejad</surname> <given-names>R</given-names>
</name>
<name>
<surname>Tavakol</surname> <given-names>S</given-names>
</name>
<name>
<surname>Ahmadi</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Roomiani</surname> <given-names>S</given-names>
</name>
<name>
<surname>Katebi</surname> <given-names>M</given-names>
</name>
</person-group>. <article-title>Autophagy, anoikis, ferroptosis, necroptosis, and endoplasmic reticulum stress: Potential applications in melanoma therapy</article-title>. <source>J Cell Physiol</source>. (<year>2019</year>) <volume>234</volume>:<page-range>19471&#x2013;9</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/jcp.28740</pub-id>
</citation>
</ref>
<ref id="B83">
<label>83</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Babaei</surname> <given-names>G</given-names>
</name>
<name>
<surname>Aziz</surname> <given-names>SG-G</given-names>
</name>
<name>
<surname>Jaghi</surname> <given-names>NZZ</given-names>
</name>
</person-group>. <article-title>EMT, cancer stem cells and autophagy; The three main axes of metastasis</article-title>. <source>BioMed Pharmacother</source>. (<year>2021</year>) <volume>133</volume>:<fpage>110909</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.biopha.2020.110909</pub-id>
</citation>
</ref>
<ref id="B84">
<label>84</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Fares</surname> <given-names>J</given-names>
</name>
<name>
<surname>Fares</surname> <given-names>MY</given-names>
</name>
<name>
<surname>Khachfe</surname> <given-names>HH</given-names>
</name>
<name>
<surname>Salhab</surname> <given-names>HA</given-names>
</name>
<name>
<surname>Fares</surname> <given-names>Y</given-names>
</name>
</person-group>. <article-title>Molecular principles of metastasis: a hallmark of cancer revisited</article-title>. <source>Signal Transduct Target Ther</source>. (<year>2020</year>) <volume>5</volume>:<fpage>28</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41392-020-0134-x</pub-id>
</citation>
</ref>
<ref id="B85">
<label>85</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Deryugina</surname> <given-names>EI</given-names>
</name>
<name>
<surname>Quigley</surname> <given-names>JP</given-names>
</name>
</person-group>. <article-title>Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature</article-title>. <source>Matrix Biol</source>. (<year>2015</year>) <volume>44&#x2013;46</volume>:<fpage>94</fpage>&#x2013;<lpage>112</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.matbio.2015.04.004</pub-id>
</citation>
</ref>
<ref id="B86">
<label>86</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Mohan</surname> <given-names>V</given-names>
</name>
<name>
<surname>Das</surname> <given-names>A</given-names>
</name>
<name>
<surname>Sagi</surname> <given-names>I</given-names>
</name>
</person-group>. <article-title>Emerging roles of ECM remodeling processes in cancer</article-title>. <source>Semin Cancer Biol</source>. (<year>2020</year>) <volume>62</volume>:<fpage>192</fpage>&#x2013;<lpage>200</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.semcancer.2019.09.004</pub-id>
</citation>
</ref>
<ref id="B87">
<label>87</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Yang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Antin</surname> <given-names>P</given-names>
</name>
<name>
<surname>Berx</surname> <given-names>G</given-names>
</name>
<name>
<surname>Blanpain</surname> <given-names>C</given-names>
</name>
<name>
<surname>Brabletz</surname> <given-names>T</given-names>
</name>
<name>
<surname>Bronner</surname> <given-names>M</given-names>
</name>
<etal/>
</person-group>. <article-title>Guidelines and definitions for research on epithelial-mesenchymal transition</article-title>. <source>Nat Rev Mol Cell Biol</source>. (<year>2020</year>) <volume>21</volume>:<page-range>341&#x2013;52</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41580-020-0237-9</pub-id>
</citation>
</ref>
<ref id="B88">
<label>88</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Liu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Xiao</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Xiao</surname> <given-names>J</given-names>
</name>
<name>
<surname>Niu</surname> <given-names>C</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>X</given-names>
</name>
<etal/>
</person-group>. <article-title>Wnt/&#x3b2;-catenin signalling: function, biological mechanisms, and therapeutic opportunities</article-title>. <source>Signal Transduct Target Ther</source>. (<year>2022</year>) <volume>7</volume>:<fpage>3</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41392-021-00762-6</pub-id>
</citation>
</ref>
<ref id="B89">
<label>89</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Viallard</surname> <given-names>C</given-names>
</name>
<name>
<surname>Larriv&#xe9;e</surname> <given-names>B</given-names>
</name>
</person-group>. <article-title>Tumor angiogenesis and vascular normalization: alternative therapeutic targets</article-title>. <source>Angiogenesis</source>. (<year>2017</year>) <volume>20</volume>:<page-range>409&#x2013;26</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1007/s10456-017-9562-9</pub-id>
</citation>
</ref>
<ref id="B90">
<label>90</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Claesson-Welsh</surname> <given-names>L</given-names>
</name>
<name>
<surname>Welsh</surname> <given-names>M</given-names>
</name>
</person-group>. <article-title>VEGFA and tumour angiogenesis</article-title>. <source>J Intern Med</source>. (<year>2013</year>) <volume>273</volume>:<page-range>114&#x2013;27</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1111/joim.12019</pub-id>
</citation>
</ref>
<ref id="B91">
<label>91</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wu</surname> <given-names>Q</given-names>
</name>
<name>
<surname>You</surname> <given-names>L</given-names>
</name>
<name>
<surname>Nepovimova</surname> <given-names>E</given-names>
</name>
<name>
<surname>Heger</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>W</given-names>
</name>
<name>
<surname>Kuca</surname> <given-names>K</given-names>
</name>
<etal/>
</person-group>. <article-title>Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape</article-title>. <source>J Hematol Oncol</source>. (<year>2022</year>) <volume>15</volume>:<fpage>77</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s13045-022-01292-6</pub-id>
</citation>
</ref>
<ref id="B92">
<label>92</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhang</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>L</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>D</given-names>
</name>
<name>
<surname>Li</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Xue</surname> <given-names>Z</given-names>
</name>
<etal/>
</person-group>. <article-title>The Role of miRNA in Tumor Immune Escape and miRNA-Based Therapeutic Strategies</article-title>. <source>Front Immunol</source>. (<year>2021</year>) <volume>12</volume>:<elocation-id>807895</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fimmu.2021.807895</pub-id>
</citation>
</ref>
<ref id="B93">
<label>93</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Biffi</surname> <given-names>G</given-names>
</name>
<name>
<surname>Tuveson</surname> <given-names>DA</given-names>
</name>
</person-group>. <article-title>Diversity and biology of cancer-associated fibroblasts</article-title>. <source>Physiol Rev</source>. (<year>2021</year>) <volume>101</volume>:<page-range>147&#x2013;76</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1152/physrev.00048.2019</pub-id>
</citation>
</ref>
<ref id="B94">
<label>94</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Salmena</surname> <given-names>L</given-names>
</name>
<name>
<surname>Poliseno</surname> <given-names>L</given-names>
</name>
<name>
<surname>Tay</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Kats</surname> <given-names>L</given-names>
</name>
<name>
<surname>Pandolfi</surname> <given-names>PP</given-names>
</name>
</person-group>. <article-title>A ceRNA hypothesis: the Rosetta stone of a hidden RNA language</article-title>? <source>Cell</source>. (<year>2011</year>) <volume>146</volume>:<page-range>353&#x2013;8</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.cell.2011.07.014</pub-id>
</citation>
</ref>
<ref id="B95">
<label>95</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ala</surname> <given-names>U</given-names>
</name>
<name>
<surname>Karreth</surname> <given-names>FA</given-names>
</name>
<name>
<surname>Bosia</surname> <given-names>C</given-names>
</name>
<name>
<surname>Pagnani</surname> <given-names>A</given-names>
</name>
<name>
<surname>Taulli</surname> <given-names>R</given-names>
</name>
<name>
<surname>L&#xe9;opold</surname> <given-names>V</given-names>
</name>
<etal/>
</person-group>. <article-title>Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments</article-title>. <source>Proc Natl Acad Sci U S A</source>. (<year>2013</year>) <volume>110</volume>:<page-range>7154&#x2013;9</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1073/pnas.1222509110</pub-id>
</citation>
</ref>
<ref id="B96">
<label>96</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>X</given-names>
</name>
<name>
<surname>Xiao</surname> <given-names>D</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>S</given-names>
</name>
<name>
<surname>Tao</surname> <given-names>Y</given-names>
</name>
</person-group>. <article-title>The chromatin-associated RNAs in gene regulation and cancer</article-title>. <source>Mol Cancer</source>. (<year>2023</year>) <volume>22</volume>:<fpage>27</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1186/s12943-023-01724-y</pub-id>
</citation>
</ref>
<ref id="B97">
<label>97</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tay</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Rinn</surname> <given-names>J</given-names>
</name>
<name>
<surname>Pandolfi</surname> <given-names>PP</given-names>
</name>
</person-group>. <article-title>The multilayered complexity of ceRNA crosstalk and competition</article-title>. <source>Nature</source>. (<year>2014</year>) <volume>505</volume>:<fpage>344</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/nature12986</pub-id>
</citation>
</ref>
<ref id="B98">
<label>98</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bartel</surname> <given-names>DP</given-names>
</name>
</person-group>. <article-title>Metazoan microRNAs</article-title>. <source>Cell</source>. (<year>2018</year>) <volume>173</volume>:<fpage>20</fpage>&#x2013;<lpage>51</lpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.cell.2018.03.006</pub-id>
</citation>
</ref>
<ref id="B99">
<label>99</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Saliminejad</surname> <given-names>K</given-names>
</name>
<name>
<surname>Khorram Khorshid</surname> <given-names>HR</given-names>
</name>
<name>
<surname>Soleymani Fard</surname> <given-names>S</given-names>
</name>
<name>
<surname>Ghaffari</surname> <given-names>SH</given-names>
</name>
</person-group>. <article-title>An overview of microRNAs: Biology, functions, therapeutics, and analysis methods</article-title>. <source>J Cell Physiol</source>. (<year>2019</year>) <volume>234</volume>:<page-range>5451&#x2013;65</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/jcp.27486</pub-id>
</citation>
</ref>
<ref id="B100">
<label>100</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Xu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Liu</surname> <given-names>X</given-names>
</name>
<name>
<surname>Jiang</surname> <given-names>J</given-names>
</name>
</person-group>. <article-title>The role of lncRNA-mediated ceRNA regulatory networks in pancreatic cancer</article-title>. <source>Cell Death Discovery</source>. (<year>2022</year>) <volume>8</volume>:<fpage>287</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41420-022-01061-x</pub-id>
</citation>
</ref>
<ref id="B101">
<label>101</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Jana</surname> <given-names>S</given-names>
</name>
<name>
<surname>Krishna</surname> <given-names>M</given-names>
</name>
<name>
<surname>Singhal</surname> <given-names>J</given-names>
</name>
<name>
<surname>Horne</surname> <given-names>D</given-names>
</name>
<name>
<surname>Awasthi</surname> <given-names>S</given-names>
</name>
<name>
<surname>Salgia</surname> <given-names>R</given-names>
</name>
<etal/>
</person-group>. <article-title>Therapeutic targeting of miRNA-216b in cancer</article-title>. <source>Cancer Lett.</source> (<year>2020</year>) <volume>484</volume>:<page-range>16&#x2013;28</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.canlet.2020.04.020</pub-id>
</citation>
</ref>
<ref id="B102">
<label>102</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Rykova</surname> <given-names>E</given-names>
</name>
<name>
<surname>Ershov</surname> <given-names>N</given-names>
</name>
<name>
<surname>Damarov</surname> <given-names>I</given-names>
</name>
<name>
<surname>Merkulova</surname> <given-names>T</given-names>
</name>
</person-group>. <article-title>SNPs in 3&#x2032;UTR miRNA target sequences associated with individual drug susceptibility</article-title>. <source>Int J Mol Sci</source>. (<year>2022</year>) <volume>23</volume>:<fpage>13725</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/ijms232213725</pub-id>
</citation>
</ref>
<ref id="B103">
<label>103</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ali Syeda</surname> <given-names>Z</given-names>
</name>
<name>
<surname>Langden</surname> <given-names>SSS</given-names>
</name>
<name>
<surname>Munkhzul</surname> <given-names>C</given-names>
</name>
<name>
<surname>Lee</surname> <given-names>M</given-names>
</name>
<name>
<surname>Song</surname> <given-names>SJ</given-names>
</name>
</person-group>. <article-title>Regulatory mechanism of microRNA expression in cancer</article-title>. <source>Int J Mol Sci</source>. (<year>2020</year>) <volume>21</volume>:<fpage>1723</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.3390/ijms21051723</pub-id>
</citation>
</ref>
<ref id="B104">
<label>104</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Qi</surname> <given-names>X</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>D-H</given-names>
</name>
<name>
<surname>Wu</surname> <given-names>N</given-names>
</name>
<name>
<surname>Xiao</surname> <given-names>J-H</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>X</given-names>
</name>
<name>
<surname>Ma</surname> <given-names>W</given-names>
</name>
</person-group>. <article-title>ceRNA in cancer: possible functions and clinical implications</article-title>. <source>J Med Genet</source>. (<year>2015</year>) <volume>52</volume>:<page-range>710&#x2013;8</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1136/jmedgenet-2015-103334</pub-id>
</citation>
</ref>
<ref id="B105">
<label>105</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Xue</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Chang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Cheng</surname> <given-names>C</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Wang</surname> <given-names>X</given-names>
</name>
<etal/>
</person-group>. <article-title>CircRNA-mediated ceRNA mechanism in Osteoarthritis: Special emphasis on circRNAs in exosomes and the crosstalk of circRNAs and RNA methylation</article-title>. <source>Biochem Pharmacol</source>. (<year>2023</year>) <volume>212</volume>:<fpage>115580</fpage>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.bcp.2023.115580</pub-id>
</citation>
</ref>
<ref id="B106">
<label>106</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Mao</surname> <given-names>M</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>J</given-names>
</name>
<name>
<surname>Xiang</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Gong</surname> <given-names>M</given-names>
</name>
<name>
<surname>Deng</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Ye</surname> <given-names>D</given-names>
</name>
</person-group>. <article-title>Role of exosomal competitive endogenous RNA (ceRNA) in diagnosis and treatment of malignant tumors</article-title>. <source>Bioengineered</source>. (<year>2022</year>) <volume>13</volume>(<issue>5</issue>):<page-range>12156&#x2013;68</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1080/21655979.2022.2073130</pub-id>
</citation>
</ref>
<ref id="B107">
<label>107</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Thomson</surname> <given-names>DW</given-names>
</name>
<name>
<surname>Dinger</surname> <given-names>ME</given-names>
</name>
</person-group>. <article-title>Endogenous microRNA sponges: evidence and controversy</article-title>. <source>Nat Rev Genet</source>. (<year>2016</year>) <volume>17</volume>:<page-range>272&#x2013;83</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/nrg.2016.20</pub-id>
</citation>
</ref>
<ref id="B108">
<label>108</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Alzahrani</surname> <given-names>AS</given-names>
</name>
</person-group>. <article-title>PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside</article-title>. <source>Semin Cancer Biol</source>. (<year>2019</year>) <volume>59</volume>:<page-range>125&#x2013;32</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.semcancer.2019.07.009</pub-id>
</citation>
</ref>
<ref id="B109">
<label>109</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ansari</surname> <given-names>D</given-names>
</name>
<name>
<surname>Ohlsson</surname> <given-names>H</given-names>
</name>
<name>
<surname>Althini</surname> <given-names>C</given-names>
</name>
<name>
<surname>Bauden</surname> <given-names>M</given-names>
</name>
<name>
<surname>Zhou</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Hu</surname> <given-names>D</given-names>
</name>
<etal/>
</person-group>. <article-title>The hippo signaling pathway in pancreatic cancer</article-title>. <source>Anticancer Res</source>. (<year>2019</year>) <volume>39</volume>:<page-range>3317&#x2013;21</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.21873/anticanres.13474</pub-id>
</citation>
</ref>
<ref id="B110">
<label>110</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hock</surname> <given-names>R</given-names>
</name>
<name>
<surname>Furusawa</surname> <given-names>T</given-names>
</name>
<name>
<surname>Ueda</surname> <given-names>T</given-names>
</name>
<name>
<surname>Bustin</surname> <given-names>M</given-names>
</name>
</person-group>. <article-title>HMG chromosomal proteins in development and disease</article-title>. <source>Trends Cell Biol</source>. (<year>2007</year>) <volume>17</volume>:<page-range>72&#x2013;9</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.tcb.2006.12.001</pub-id>
</citation>
</ref>
<ref id="B111">
<label>111</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Dahl</surname> <given-names>M</given-names>
</name>
<name>
<surname>Husby</surname> <given-names>S</given-names>
</name>
<name>
<surname>Eskelund</surname> <given-names>CW</given-names>
</name>
<name>
<surname>Besenbacher</surname> <given-names>S</given-names>
</name>
<name>
<surname>Fjelstrup</surname> <given-names>S</given-names>
</name>
<name>
<surname>C&#xf4;me</surname> <given-names>C</given-names>
</name>
<etal/>
</person-group>. <article-title>Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma: a study of younger patients from the MCL2 and MCL3 clinical trials</article-title>. <source>Leukemia</source>. (<year>2022</year>) <volume>36</volume>:<page-range>177&#x2013;88</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1038/s41375-021-01311-4</pub-id>
</citation>
</ref>
<ref id="B112">
<label>112</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Huang</surname> <given-names>M</given-names>
</name>
<name>
<surname>He</surname> <given-names>Y-R</given-names>
</name>
<name>
<surname>Liang</surname> <given-names>L-C</given-names>
</name>
<name>
<surname>Huang</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>Z-Q</given-names>
</name>
</person-group>. <article-title>Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer</article-title>. <source>World J Gastroenterol</source>. (<year>2017</year>) <volume>23</volume>:<page-range>6330&#x2013;8</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.3748/wjg.v23.i34.6330</pub-id>
</citation>
</ref>
<ref id="B113">
<label>113</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Zhao</surname> <given-names>T</given-names>
</name>
<name>
<surname>Zheng</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Hao</surname> <given-names>D</given-names>
</name>
<name>
<surname>Jin</surname> <given-names>X</given-names>
</name>
<name>
<surname>Luo</surname> <given-names>Q</given-names>
</name>
<name>
<surname>Guo</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Blood circRNAs as biomarkers for the diagnosis of community-acquired pneumonia</article-title>. <source>J Cell Biochem</source>. (<year>2019</year>) <volume>120</volume>:<page-range>16483&#x2013;94</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1002/jcb.28863</pub-id>
</citation>
</ref>
<ref id="B114">
<label>114</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Song</surname> <given-names>R</given-names>
</name>
<name>
<surname>Bai</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Li</surname> <given-names>X</given-names>
</name>
<name>
<surname>Zhu</surname> <given-names>J</given-names>
</name>
<name>
<surname>Zhang</surname> <given-names>H</given-names>
</name>
<name>
<surname>Shi</surname> <given-names>Y</given-names>
</name>
<etal/>
</person-group>. <article-title>Plasma circular RNA DYM related to major depressive disorder and rapid antidepressant effect treated by visual cortical repetitive transcranial magnetic stimulation</article-title>. <source>J Affect Disord</source>. (<year>2020</year>) <volume>274</volume>:<page-range>486&#x2013;93</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.jad.2020.05.109</pub-id>
</citation>
</ref>
<ref id="B115">
<label>115</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chatterjee</surname> <given-names>N</given-names>
</name>
<name>
<surname>Bivona</surname> <given-names>TG</given-names>
</name>
</person-group>. <article-title>Polytherapy and targeted cancer drug resistance</article-title>. <source>Trends Cancer</source>. (<year>2019</year>) <volume>5</volume>:<page-range>170&#x2013;82</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1016/j.trecan.2019.02.003</pub-id>
</citation>
</ref>
</ref-list>
<glossary>
<title>Glossary</title>
<def-list>
<def-item>
<term>ncRNA</term>
<def><p>non-coding RNA</p></def>
</def-item>
<def-item>
<term>circRNA</term>
<def><p>circular RNAs</p></def>
</def-item>
<def-item>
<term>ceRNA</term>
<def><p>competitive endogenous RNA</p></def>
</def-item>
<def-item>
<term>HDV</term>
<def><p>hepatitis delta virus</p></def>
</def-item>
<def-item>
<term>pol II</term>
<def><p>polymerase II</p></def>
</def-item>
<def-item>
<term>TF</term>
<def><p>transcription factor</p></def>
</def-item>
<def-item>
<term>TAH</term>
<def><p>transcriptionally activated to a higher level than the host genes</p></def>
</def-item>
<def-item>
<term>SE</term>
<def><p>super enhancer</p></def>
</def-item>
<def-item>
<term>iRegulon</term>
<def><p>the intragenic regulon</p></def>
</def-item>
<def-item>
<term>nt</term>
<def><p>nucleotide</p></def>
</def-item>
<def-item>
<term>EcircRNAs</term>
<def><p>exonic circRNAs</p></def>
</def-item>
<def-item>
<term>CiRNAs</term>
<def><p>intronic circRNAs</p></def>
</def-item>
<def-item>
<term>EIciRNAs</term>
<def><p>exon&#x2013;intron circRNAs</p></def>
</def-item>
<def-item>
<term>tricRNAs</term>
<def><p>tRNA introns cirRNAs</p></def>
</def-item>
<def-item>
<term>miRNA</term>
<def><p>microRNA</p></def>
</def-item>
<def-item>
<term>miR</term>
<def><p>mircoRNA</p></def>
</def-item>
<def-item>
<term>snRNP</term>
<def><p>small nuclear ribonucleoprotein</p></def>
</def-item>
<def-item>
<term>UBAP2</term>
<def><p>ubiquitin-associated protein 2</p></def>
</def-item>
<def-item>
<term>RNase R</term>
<def><p>ribonuclease R</p></def>
</def-item>
<def-item>
<term>DR</term>
<def><p>diabetic retinopathy</p></def>
</def-item>
<def-item>
<term>OA</term>
<def><p>osteoarthritis</p></def>
</def-item>
<def-item>
<term>PE</term>
<def><p>preeclampsia</p></def>
</def-item>
<def-item>
<term>TC</term>
<def><p>thyroid cancer</p></def>
</def-item>
<def-item>
<term>EC</term>
<def><p>esophageal cancer</p></def>
</def-item>
<def-item>
<term>NSCLC</term>
<def><p>non-small cell lung cancer</p></def>
</def-item>
<def-item>
<term>BC</term>
<def><p>breast cancer</p></def>
</def-item>
<def-item>
<term>TNBC</term>
<def><p>triple-negative breast cancer</p></def>
</def-item>
<def-item>
<term>HCC</term>
<def><p>hepatocellular carcinoma</p></def>
</def-item>
<def-item>
<term>CRC</term>
<def><p>colorectal cancer</p></def>
</def-item>
<def-item>
<term>OC</term>
<def><p>ovarian cancer</p></def>
</def-item>
<def-item>
<term>CC</term>
<def><p>cervical cancer</p></def>
</def-item>
<def-item>
<term>GC</term>
<def><p>gastric cancer</p></def>
</def-item>
<def-item>
<term>RCC</term>
<def><p>renal cell carcinoma</p></def>
</def-item>
<def-item>
<term>PAAD</term>
<def><p>pancreatic adenocarcinoma</p></def>
</def-item>
<def-item>
<term>PDAC</term>
<def><p>pancreatic ductal adenocarcinoma</p></def>
</def-item>
<def-item>
<term>qRT-PCR</term>
<def><p>quantitative real-time polymerase chain reaction</p></def>
</def-item>
<def-item>
<term>CCK-8</term>
<def><p>cell counting Kit-8</p></def>
</def-item>
<def-item>
<term>EDU</term>
<def><p>ethylenediurea</p></def>
</def-item>
<def-item>
<term>PCNA</term>
<def><p>proliferating cell nuclear antigen</p></def>
</def-item>
<def-item>
<term>CDK</term>
<def><p>cyclin-dependent kinase</p></def>
</def-item>
<def-item>
<term>EMT</term>
<def><p>epithelial-mesenchymal transition</p></def>
</def-item>
<def-item>
<term>ECM</term>
<def><p>extracellular matrix</p></def>
</def-item>
<def-item>
<term>TME</term>
<def><p>tumor microenvironment</p></def>
</def-item>
<def-item>
<term>CAFs</term>
<def><p>cancer-associated fibroblasts</p></def>
</def-item>
<def-item>
<term>TAMs</term>
<def><p>tumor associated macrophages</p></def>
</def-item>
<def-item>
<term>pri-miRNAs</term>
<def><p>primary-microRNAs</p></def>
</def-item>
<def-item>
<term>pre-miRNAs</term>
<def><p>precursor-miRNAs</p></def>
</def-item>
<def-item>
<term>dsRNA</term>
<def><p>double-stranded RNA</p></def>
</def-item>
<def-item>
<term>AGO</term>
<def><p>Argonaute</p></def>
</def-item>
<def-item>
<term>RISC</term>
<def><p>RNA-induced silencing complex</p></def>
</def-item>
<def-item>
<term>3&#x2032;UTR</term>
<def><p>3&#x2032; untranslated region</p></def>
</def-item>
<def-item>
<term>DDP</term>
<def><p>diamminedichloroplatinum/cisplatin</p></def>
</def-item>
<def-item>
<term>GEO</term>
<def><p>Gene Expression Omnibus</p></def>
</def-item>
<def-item>
<term>TNM</term>
<def><p>tumor-node-metastasis</p></def>
</def-item>
<def-item>
<term>OS</term>
<def><p>overall survival</p></def>
</def-item>
<def-item>
<term>RFS</term>
<def><p>recurrence-free survival</p></def>
</def-item>
<def-item>
<term>TTR</term>
<def><p>time to recurrence</p></def>
</def-item>
<def-item>
<term>DMFS</term>
<def><p>distant metastasis-free survival</p></def>
</def-item>
<def-item>
<term>DXR</term>
<def><p>doxorubicin</p></def>
</def-item>
<def-item>
<term>IL</term>
<def><p>interleukin</p></def>
</def-item>
<def-item>
<term>ECMO</term>
<def><p>extracorporeal membrane oxygenation</p></def>
</def-item>
<def-item>
<term>hRMECs</term>
<def><p>human retinal microvascular endothelial cells</p></def>
</def-item>
<def-item>
<term>MAPK</term>
<def><p>mitogen-activated protein kinase</p></def>
</def-item>
<def-item>
<term>ERK</term>
<def><p>extracellular signal-regulated kinase</p></def>
</def-item>
<def-item>
<term>JNK</term>
<def><p>jun N-terminal kinase</p></def>
</def-item>
<def-item>
<term>FGF9</term>
<def><p>fibroblast growth factor 9</p></def>
</def-item>
<def-item>
<term>APC/C</term>
<def><p>anaphase-promoting complex/cyclosome</p></def>
</def-item>
<def-item>
<term>SCF</term>
<def><p>SKP1-Cullin-F-box</p></def>
</def-item>
<def-item>
<term>SOX4</term>
<def><p>SRY-related high-mobility-group box 4</p></def>
</def-item>
<def-item>
<term>c-IAP1</term>
<def><p>cellular inhibitors of apoptosis 1</p></def>
</def-item>
<def-item>
<term>LC3B</term>
<def><p>light chain 3B</p></def>
</def-item>
<def-item>
<term>ATG</term>
<def><p>autophagy-related</p></def>
</def-item>
<def-item>
<term>FOXO1</term>
<def><p>forkhead box transcription factor O1</p></def>
</def-item>
<def-item>
<term>MMPs</term>
<def><p>matrix metalloproteinases</p></def>
</def-item>
<def-item>
<term>&#x3b1;-SMA</term>
<def><p>alpha-smooth muscle actin</p></def>
</def-item>
<def-item>
<term>KLF4</term>
<def><p>kruppel-like factor 4</p></def>
</def-item>
<def-item>
<term>RAC1</term>
<def><p>ras-related C3 botulinum toxin substrate 1</p></def>
</def-item>
<def-item>
<term>FAK</term>
<def><p>focal adhesion kinase</p></def>
</def-item>
<def-item>
<term>LGR4</term>
<def><p>leucine-rich repeat-containing G protein&#x2013;coupled receptor 4</p></def>
</def-item>
<def-item>
<term>VEGF</term>
<def><p>vascular endothelial growth factor</p></def>
</def-item>
<def-item>
<term>CXCL</term>
<def><p>C-X-C chemokine ligand</p></def>
</def-item>
<def-item>
<term>CXCR</term>
<def><p>C-X-C chemokine receptor</p></def>
</def-item>
<def-item>
<term>ZEB1</term>
<def><p>zinc finger E-box binding homeobox 1</p></def>
</def-item>
<def-item>
<term>HIF</term>
<def><p>hypoxia-inducible factor</p></def>
</def-item>
<def-item>
<term>SDC1</term>
<def><p>syndecan-1</p></def>
</def-item>
<def-item>
<term>IFIT</term>
<def><p>tetratricopeptide repeats</p></def>
</def-item>
<def-item>
<term>DGCR8</term>
<def><p>DiGeorge syndrome critical region gene 8</p></def>
</def-item>
<def-item>
<term>TNRC6</term>
<def><p>trinucleotide repeat containing 6</p></def>
</def-item>
<def-item>
<term>PI3K</term>
<def><p>phosphatidylinositol-3 kinase</p></def>
</def-item>
<def-item>
<term>mTOR</term>
<def><p>mammalian target of rapamycin</p></def>
</def-item>
<def-item>
<term>YAP</term>
<def><p>yes-associated protein</p></def>
</def-item>
<def-item>
<term>HMG</term>
<def><p>high-mobility group</p></def>
</def-item>
<def-item>
<term>CHD2</term>
<def><p>chromodomain helicase DNA binding protein 2</p></def>
</def-item>
<def-item>
<term>ASF1B</term>
<def><p>anti-silencing function 1B</p></def>
</def-item>
<def-item>
<term>SEMA6D</term>
<def><p>semaphorin 6D</p></def>
</def-item>
<def-item>
<term>KAT6B</term>
<def><p>lysine acetyltransferase 6B</p></def>
</def-item>
<def-item>
<term>STAT1</term>
<def><p>signal transducer and activator of transcription 1</p></def>
</def-item>
<def-item>
<term>RNF2</term>
<def><p>ring finger protein 2</p></def>
</def-item>
<def-item>
<term>eNOS</term>
<def><p>endothelial nitric oxide synthases</p></def>
</def-item>
<def-item>
<term>TNF&#x3b1;</term>
<def><p>tumor necrosis factor &#x3b1;</p></def>
</def-item>
<def-item>
<term>MCP-1</term>
<def><p>monocyte chemoattractant protein- 1</p></def>
</def-item>
<def-item>
<term>EGR1</term>
<def><p>early growth response factor 1</p></def>
</def-item>
<def-item>
<term>WNT5B</term>
<def><p>wingless-type MMTV integration site family, member 5B</p></def>
</def-item>
<def-item>
<term>FOXM1</term>
<def><p>forkhead box protein M1</p></def>
</def-item>
</def-list>
</glossary>
</back>
</article>