Previous evidence proved that both circRNAs and autophagy possess high conservation and whether the circRNA–autophagy network plays pro- or anti-neoplasm effects is dependent on cancer type, pathological grade, clinical stage, and even exogenous stimuli (Kristensen et al., 2019; Zhou et al., 2021a). Hence, we believe it is essential to illustrate the circRNA–autophagy regulative system in specific malignancies, which was overviewed in Figure 3.

Globally, lung cancer is the leading cause of all cancer-related deaths (Siegel et al., 2021; Sung et al., 2021), with non-small cell lung cancer (NSCLC) accounting for more than 85% of the newly diagnosed lung cancer cases (Herbst et al., 2018). Meanwhile, both circRNAs and autophagy are regarded as important modulators for the progression of NSCLC. Recent evidence found that circ_0010235, circ-FOXM1, circ_0085131, circ_0003028, circ_100565, circHIPK3, and circ_0020123 were all identified with high expressions in NSCLC cell lines or clinical samples and play tumor-genetic roles (Chen et al., 2020; Kong, 2020; Zhong et al., 2021a; Zhang et al., 2021b; Guan et al., 2021; Wei et al., 2021). Sponging effect is the mainstream regulating mechanism. Specifically, circ_0010235 sponged miR-433-3p to regulate the TIPRL levels, promoting the proliferation, autophagy, and migration of NSCLC (Zhang et al., 2021b); circ-FOXM1 and circ_0020123 exerted similar effects through the miR-149-5p/ATG5 and miR-512-3p/CORO1C axis, respectively (Wei et al., 2021; Zhang et al., 2022). In addition, cisplatin (DDP)-based chemotherapy has long been performed as an important adjuvant treatment for lung cancer, while DDP resistance in NSCLC brings great challenges to its curative effects. Silence of circ_0085131 was reported to inhibit the autophagy process through the miR‐654‐5p/ATG7 axis (Kong, 2020), which resulted in the increase in the sensitivity of NSCLC to DDP. Knockdown of circ_100565 can also restrain autophagy to mitigate the DDP resistance through sponging the miR-377-3p to upregulate the ADAM28 level, therefore providing a novel approach to deal with DDP resistance (Zhong et al., 2021a).

Notably, although circ_0003028 was proved to facilitate the proliferation, metastasis, and angiogenesis of NSCLC via modulation of the miR-1298-5p/GOT2 axis, the silence of circ_0003028 exhibited a promoting effect on autophagy, implying that circ_0003028 played an inhibitive role in autophagy (Guan et al., 2021). Intriguingly, circHIPK3 was exhibited to sponge miR-124-3p to regulate the downstream STAT3-PRKAA/AMPKα pathway, exerting a suppressive effect on autophagy in the A549 and H838 cell lines (STK11 mutant cell lines), while the facilitating role of circHIPK3 on autophagy was observed in H1299 cells (STK11 wild-type cell line), which was mediated through the promotive effect of circHIPK3 on STK11 (Chen et al., 2020).

Pathologically, esophageal carcinoma consists of ESCC and esophageal adenocarcinoma (EAC), with the former accounting for nearly 88% of esophageal carcinoma cases (Murphy et al., 2017; Abnet et al., 2018). Large amounts of ncRNAs have been found to play crucial roles in the modulation of ESCC development (Feng et al., 2019). For example, Meng et al. (2020) proved that ciRS-7 was over-expressed in ESCC cell lines and tissues, playing an inhibitive role in rapamycin and starvation-induced autophagy. Furthermore, miR-1299 was shown to be sponged by ciRS-7 and exerted the effect of interfering with EGFR mRNA expression level by combining to the 3’UTR region of the EGFR mRNA followed by the EGFR-Akt-mTOR pathway effectively regulated, as well as the downstream autophagy process.

Despite the great advances in treatment, patients suffering from GC mostly have an undesirable overall survival time, partly resulting from the late stage of GC at diagnosis (Peng et al., 2020). Both ncRNAs and autophagy were found to be the crucial regulators in the progression of GC (Wei et al., 2020; Xu et al., 2020; Rahman et al., 2021).

Over-expressed circKIAA0907 inhibited the proliferation, cell cycle, and cell autophagy in GC. Dual-luciferase report assays presented that circKIAA0907 sponged miR-452-5p, which negatively modulated the downstream KTA6B protein, weakening the repressive effects of circKIAA0907 in GC (Zhu et al., 2020). Moreover, circ_0032821 was proved to be highly expressed in GC tissues and cells, significantly associated with high clinical stages and poor prognostic results. Silence of circ_0032821 restrained the proliferation, EMT process, migration, and invasion, while enhancing the autophagy of GC cells. On the contrary, when circ_0032821 was over-expressed, the abovementioned phenotypes showed opposite trends, further confirming the oncogenetic roles of circ_0032821. The following explorations demonstrated that circ_0032821 activated the MEK1/ERK1/2 pathway to exert biological effects, while the specific mechanism of the activation of this axis was not discussed (Jiang et al., 2020).

Moreover, there have been large amounts of research studies demonstrating the roles of the circRNA–autophagy network in drug-resistant GC cells. For instance, Sun et al. (2020) found that circMCTP2 was notably repressed in the cisplatin (DDP)-resistant GC cells, and a high level of circMCTP2 predicted pleasant prognostic results. Moreover, the over-expressed circMCTP2 was proved to inhibit proliferation and autophagy while enhancing the sensitivity of GC cells to DDP. Further experiments proved that circMCTP2 bound miR-99a-5p through a competing endogenous RNA (ceRNA) mechanism to regulate the MTMR3 protein and exerted the abovementioned effects. Peng et al. (2020) also identified a low-expressed circCUL2 in GC tissue and cells, which was proved to repress the viability, autophagy, and metastasis of GC cells. Following experiments demonstrated that circCUL2 combined with miR-142-3p to modulate ROCK2 levels to interfere in the autophagy process, finally reducing the DDP resistance of GC cells.

Additionally, apatinib, a small molecular antiangiogenetic targeted agent, was proven to be safe and effective for GC patients when combined with oxaliplatin (Lin et al., 2021). Ma et al. (2020) presented that apatinib increased the levels of circRACGAP1 in GC cells, which sponged miR-3657 to regulate ATG expression and further induced autophagy to enhance GC cell resistance to apatinib. Therefore, silencing circRACGAP1 and inhibiting autophagy hold great potential for reinforcing the efficacy of apatinib in GC.

Almost all the cells could secret exosomes (Davis, 2016), and the circRNAs carried by exosomes were recognized as crucial regulators of distant malignant cells (Zhou et al., 2021b; Li et al., 2022). Yao et al. (2021) collected the serum of DDP-resistant GC patients and the culture medium of DDP-resistant GC cells, then identified the highly expressed circPVT1 in the exosomes of the abovementioned two systems. Knockdown of circPVT1 significantly refrained the autophagy and viability and increased the sensitivity of GC cells to DDP. Following rescue experiments proved that circPVT1 activates cell autophagy by regulating the miR-30a-5p/YAP1 axis. Similarly, Yang et al. (2021a) illustrated that circUBE2Q2 was highly expressed in GC cells and clinical samples and could be transported elsewhere by exosomes. Repression of circUBE2Q2 refrained the proliferation, glycolysis, invasion, and migration, while activating autophagy in GC cells. Further studies indicated that circUBE2Q2 sponged miR-370-3p to regulate the level of STAT3, exerting the abovementioned biological effects. Moreover, Zhang et al. (2019) found the upregulated circNRIP1 through the next generation sequencing of GC tissues and proved the promotive effect of circNRIP1 on the development of GC. miR-149-5p was regulated by circNRIP1 through a ceRNA mechanism and modulated the AKT1 level to influence the autophagy process. Exosomes carrying circNRIP1 were also proved to enhance the EMT and metastasis of GC cells in animal models.

In the female population, the number of annual new BC cases has surpassed that of lung cancer, becoming the most common malignancy (Sung et al., 2021). In particular, triple negative BC (TNBC) accounts for nearly 15% of all BC cases and is recognized as the most lethal BC due to its fast progression, high metastasis, and recurrence rate (Almansour, 2022; Derakhshan and Reis-Filho, 2022).

Zheng et al. (2020) identified the highly expressed circSEPT9 in TNBC cells and tissues, which positively correlated to the high clinical stages and poorer prognostic outcomes. Silencing of circSEPT9 played a repressive role in the proliferation and metastasis of TNBC cells, while activating autophagy. Subsequent experiments demonstrated that circSEPT9 sponged miR-637 to regulate the downstream target LIF/Stat3 signal pathway to exert the abovementioned effects. In addition, Liang et al. (2020) found high autophagy levels positively correlated to poorer clinical prognosis outcomes and identified the autophagy-related circCDYL. Over-expressed circCDYL was demonstrated to promote the autophagy process as well as the malignant biological behaviors, which were proved to be mediated via the downstream miR-1275-ATG7/ULK1 axis.

TNBC was found not sensitive to some anthracycline chemotherapy medicines (Chen et al., 2014), in which the circRNA–autophagy axis may play essential roles. For example, Li et al. (2021b) confirmed the existence of circAKT3, which was highly regulated in TNBC cells and tissues, positively related to increased tumor size, high clinical stages, and poorer prognostic outcomes. Over-expressed circAKT3 was proved to enhance the resistance of TNBC to DDP, ADM, PTX, and GEM. Following experiments demonstrated that circAKT3 could bind to miR-206 and miR-613 to interfere with their inhibition of the targeted PI3K/Akt/mTOR pathway, thus inhibiting the TNBC cell autophagy (Li et al., 2021b). Yang et al. (2020) attempted to explore the roles of highly regulated circABCB10 in BC cells (Liang et al., 2017) and demonstrated that silencing of circABCB10 markedly inhibited the resistance of BC cells to PTX as well as cell viability, invasion, and autophagy. Subsequent experiments suggested circABCB10 combined let-7a-5p to modulate downstream DUSP7 and further exerted the abovementioned effects (Yang et al., 2020). Based on previous research (Gao et al., 2019a), Liu et al. (2020a) attempted to investigate the roles of circ_0006528 in PTX-resistant BC cells. Results demonstrated that circ_0006528 was highly regulated in PTX-resistant BC cell lines. Inhibition of circ_0006528 notably suppressed the viability, metastasis, and cell autophagy of PTX-resistant BC cells. The following results suggested that miR-1299 could be combined with circ_0006528 to attenuate the inhibition of the CDK8 expression, thereby mediating the abovementioned roles of circ_0006528. Wang et al. (2021a) confirmed that upregulated circ_0092276 promoted ADM resistance by activating the autophagy process in BC cells. The functioning mechanism was sponging miR-348 to upregulate ATG7, which is one of the key genes in the autophagic pathway. Following experiments demonstrated that activated autophagy greatly contributed to its ADM resistance.

circRNAs could also directly bind to specific proteins to regulate their functions in BC (Salzman et al., 2012). For instance, circDNMT1 was upregulated in BC cell lines and clinical samples, with over-expression of circDNMT1, proved to enhance autophagy-mediated proliferation and viability. Meanwhile, circDNMT1 had the potency to combine with p53 protein to promote the relocation of p53 into cell nuclei, leading to the enhancement of cell autophagy and then subsequently enhanced cell viability. On the other hand, circDNMT1 could bind with AUF1 protein and promote the latter transported into cell nuclei, resulting in the inhibition of p53 expression. As p53 is an essential cancer suppressor (Du et al., 2018), circDNMT1 could also exert promotive effects on BC through the abovementioned mechanisms.

Globally, primary hepatic carcinoma is the sixth most common and the third most deadly malignancy (Siegel et al., 2021; Sung et al., 2021). Pathologically, HCC accounts for 75–85% of all hepatic carcinoma cases (Janevska et al., 2015; Benson et al., 2021).

Sorafenib, a novel medicine with multiple targets, was widely applied for the treatment of late renal and liver cancers (Zhu et al., 2011). Liu et al. (2020b) identified a highly regulated circ_0008367 in sorafenib-treated HCC cells and demonstrated that circ_0008367 enhances cell autophagy and ferroptosis to mitigate the resistance of HCC cells to sorafenib. Further investigations suggested circ_008367 played the abovementioned roles through directly binding to ALKBH5 protein (Guo et al., 2018; Liu et al., 2020b), which was recognized as an autophagy inhibitor (Zhu et al., 2019). Matrine is a type of herbal compound with various biological effects, including suppressing the development of glioma and melanoma (Zhang et al., 2018; Zhou et al., 2018). Based on previous research (Lin et al., 2020), Lin et al. (2020) found that matrine markedly lowered the levels of circ_0027345, inducing cell apoptosis and autophagy in HCC cells. Furthermore, over-expressed circ_0027345 could regulate the miR-345-3p/HOXD3 pathway to inhibit the autophagy process, resulting in attenuation of the anti-tumor effect of matrine in HCC cells. In addition, circRNAs also mediate the effects of chemical compounds in the living cells. For example, Hao et al. (2020) proved that cadmium chloride upregulated the level of circ_0040768, which enhanced cell autophagy. Also, phenylethyl caffeate was proved to suppress the level of circ_0040768 and thus interfering the cadmium chloride from exerting toxic effects, providing a potential direction for the treatment of chromium poisoning. Meanwhile, Zhang et al. (2020a) found that H₂O₂ induced the downregulation of circSPECC1 in HCC, which was proved to interact with miR-33a to inhibit downstream autophagy, further promoting the progression of HCC in an oxidative situation, while the mechanism of miR-33a regulating autophagy was uninvestigated in this research.

In the global male population, PCA is the second most common and fifth most lethal cancer, depriving the lives of more than 370,000 patients every year (Mottet et al., 2021; Sung et al., 2021). The group of Chuanfang Zhong identified the autophagy-related circ_0001747 and proved that high levels of circ_0001747 positively correlated with a lower risk of biological recurrence of PCA. Silencing of circ_0001747 could activate the viability and autophagy of PCA cells (Zhong et al., 2021b). Lu et al. (2021) identified the upregulated circCSPP1 in PCA tissues and proved that high levels of circCSPP1 significantly enhanced the autophagy process as well as the proliferative and metastatic capability of PCA cells. miR-520h could be bound by circCSPP1 and affect the EGR1 expression to mediate the abovementioned effects. Yu et al. (2022) identified highly expressed circCEMIP in PCA cells and tissues, which functioned as a miR-1248 sponge to regulate downstream TM9SF4 protein expression level, further inhibiting mTOR phosphorylation and facilitating the autophagy process. Following experiments indicated that enhanced autophagy protected PCA cells from anoikis, accelerating PCA progression.

Radiotherapy plays an important role in the treatment of PCA, and the radical radiation therapy of PCA is markedly associated with the pleasant survival outcomes of PCA patients (Tharmalingam et al., 2019; Philippou et al., 2020). Through a review of previous research studies, Cai et al. (2022) learned that circCCNB2 could enhance the sensitivity of renal cell carcinoma to chemotherapy; therefore, they attempted to investigate whether circCCNB2 had similar effects in the radio-resistance of PCA. Following experiments demonstrated that circCCNB2 was upregulated in radio-resistant PCA cells, and silencing of circCCNB2 inhibited cell autophagy to increase the sensitivity of PCA cells to radiotherapy. miR-30b-5p could be combined with circCCNB2 and function as a regulator of KIF18A to mediate the abovementioned effects of circCCNB2 (Cai et al., 2022).

Patients with BLCA usually suffer from a high rate of recurrence and poor clinical prognosis, especially for muscle-invasive bladder cancer (MIBC) (Flaig et al., 2018; Patel et al., 2020). The circRNA–autophagy network plays a crucial role in the progression of BLCA. Zhang et al. (2021c) identified upregulated circ_0007813 in BLCA tissues and proved that high expression of circ_0007813 significantly related to larger tumor size as well as higher clinical and pathological stages, predicting poorer clinical outcomes. Following experiments demonstrated that circ_0007813 was combined with miR-361-3p to regulate downstream IGF2R, further inhibiting the autophagy process of BLCA cells.

Nearly 60–85% of renal carcinoma cases are pathologically diagnosed as RCC, among which 25% of cases are presented with distant metastasis at diagnosis (Chewcharat et al., 2019; Usher-Smith et al., 2020). Li et al. (2020a) learned about the abnormal expression of circ_0054537 in RCC and confirmed that repression of circ_0054537 observably suppressed the proliferation, metastasis, autophagy, and glycolysis of RCC cells, which was proved to be mediated by the miR-640/NPTX2 axis (Pei et al., 2021). Yan et al. (2019) identified upregulated circ_0035483 in RCC cells, which was proved to reinforce the autophagy of RCC cells through modulating the miR-335/CCNB1 axis. Moreover, the enhanced autophagy was shown to increase the viability of RCC in the administration of gemcitabine. Therefore, lowering the expression of circ_0035483 provides an inspiring strategy for combating gemcitabine resistance of RCC cells.

Globally, cervical cancer has become the most common malignancy type in 23 regions and the most lethal cancer type in 36 regions (Sung et al., 2021). To further understand this disease, Tang et al. (2019), Guo et al. (2019), and Zhang and Zhang (2020) identified upregulated circ_0000515, circ_0023404, and circ_0000285 from cervical cancer tissue and cells, respectively. All the abovementioned circRNAs were proven to accelerate the growth and metastasis of cervical cancer, functioning through sponging miR-326 (targeting ELK1 mRNA), miR-5047, and miR-197-3p (targeting ELK1 mRNA), respectively. Notably, all these three circRNAs played an inhibitive role in the autophagy process. In addition, circ_0023404 also facilitated angiogenesis and DDP resistance in cervical cancer (Guo et al., 2019). Likewise, Jingjing Guo et al. also confirmed the highly expressed circMTO1, which presented effects of promoting the proliferative and metastatic potential of cervical cancer cells. Also, the miR-6893/S100A1 axis has been shown to mediate the aforementioned effects. In particular, circMTO1 activated the autophagy of cervical cancer cells and further enhanced the DDP resistance of cervical cancer cells (Chen et al., 2019).

Annually, 10% of the newly diagnosed malignancy cases are proven to be colorectal cancer (Dekker et al., 2019), which ranks second in both the male and female population (Siegel et al., 2020).

The research group of Zhang et al. (2021d), Chen et al. (2021), and Xie et al. (2021), respectively, identified the upregulated circ_103948, circ_UBAP2, and circ_BANP in the CRC tissues and cells, and the following experiments proved that all the aforementioned circRNAs possessed the capability of promoting the colorectal cancer proliferation and metastasis. In particular, circBANP was shown to promote the radiation resistance of CRC. In terms of autophagy, circ_103948 presented obviously inhibitive effects, while the other two circRNAs were proved promotive. Subsequent experiments suggested circ_103948, circ_UBAP2, and circ_BANP could modulate miR-1236-3p/TPT1, miR-338-3p, and miR-582-5p/FOXO1 axis through the ceRNA mechanism, respectively, to exert the relevant biological effects.

Furthermore, Feng et al. (2020) also found that the hypoxic microenvironment could induce the high expression of circCCDC66, which enhanced autophagy and thus strengthened the proliferative and metastatic capability of CRC cells under a hypoxic environment.

With the insidious onset, PDAC is usually found at the late stage of diagnosis, leading to a tumor that is unresectable through surgical method (Pant et al., 2019; Ho et al., 2020). Yang et al. (2021b) identified highly expressed circRHOBTB3 in PDAC cells and tissues, and their research suggested that circRHOBTB3 accelerated the viability and proliferation of PDAC cells, which was mediated by the circRHOBTB3-activated autophagy. Subsequent experiments demonstrated that circRHOBTB3 sponged miR-600 to upregulate the NACC1 expression, which further activated the Akt/mTOR pathway to induce cell autophagy. Meanwhile, He et al. (2022) discovered upregulation of circATG7 in PDAC tissue, which stabilized autophagy-related 7 (ATG7) mRNA by recruiting HUR and sponging miR-766-5p, a suppressor of ATG7 mRNA, thus increasing the expression of ATG7, which promotes the autophagy process.

Ovarian cancer is the most lethal gynecological malignancy (Hurwitz et al., 2021; Sung et al., 2021), and epithelial ovarian cancer (EOC) accounts for 95% of all ovarian cancer cases (Lheureux et al., 2019).

Gan et al. (2020) identified upregulated circEEF2 and circMUC16 from EOC tissues and cells, both of which promoted the proliferation and metastasis of EOC cells, as well as cell autophagy. Specifically, circEEF2 has been shown to combine with miR-6881-3p and modulate the downstream proteins, including ATG7 and ATG5, promoting autophagy course. Furthermore, circEEF2 was also proved to directly bind with ANXA2 protein, which could inhibit mTOR levels, resulting in enhanced autophagy (Yong et al., 2020). On the other hand, circMUC16 has been shown to sponge miR-199a, which could bind to mRNA of Beclin 1 and RUNX1 genes. CircMUC16 attenuated the inhibitive effect of miR-199a on Beclin 1 and RUNX1, exerting the promotive effect on autophagy. Further experiments also suggested that circMUC16 is directly bound to ATG13, contributing to enhanced autophagy.

Zhang et al. (2021a) identified upregulated circRAB11FIP1 from Torin1-pretreated EOC cells, which was proven to be highly expressed in EOC tissues (Lheureux et al., 2019). Silence of circRAB11FIP1 blocked the autophagic flux of EOC cells, while over-expressed circRAB11FIP1 exerted the promotive effect on autophagy and thus enhanced the proliferation and metastasis of EOC cells. Further experiments demonstrated that circRAB11FIP1 sponged miR-129 to upregulate ATG7 and ATG14, mediating the autophagy process. Moreover, circRAB11FIP1 has been shown to bind with FTO mRNA to enhance the FTO proteins, which could promote autophagy through methylation of m6A in ATG7 and ATG5 mRNAs.

With a high metastatic potential and malignant behaviors (Brodeur and Bagatell, 2014; Fletcher et al., 2018), NB presents poor prognostic outcomes, especially for junior patients of more than 18 months (DuBois and Park, 2018). Zhu et al. (2021a) identified high-regulated circ_0013401 in NB tissues and cells, the silence of which refrained the growth and metastasis of NB tissues but enhanced autophagy and apoptosis of NB cells. Further experiments demonstrated that circ_0013401 combined with miR-195 to regulate PAK2 expression.

RB is the most common intraocular tumor in infants and children (Broaddus et al., 2009). In RB cells, circ_0000034 downregulated miR-361-3p, a tumor suppressor, by a sponge mechanism (Liu et al., 2020c). Since the downstream gene of miR-361-3p, STX17, promoted the formation of autophagosomes, it is indicated that circ_0000034 accelerated the progress of RB by promoting the autophagy process.

Glioma is the most frequently occurring malignancy of the brain in adult patients, with glioblastoma (GBM) as the worst malignant pathological type (Tan et al., 2020; Yuan et al., 2022). Yuan et al. (2022) identified downregulated circ_0072309 in GBM and proved that over-expressed circ_0072309 upregulated RNF144B protein levels via sponging miR-100, leading to a decrease in ubiquitin-mediated p53 degradation, which enhanced autophagic cell death and TMZ sensitivity of GBM cells.

Osteosarcoma is the most common malignancy in the orthopedics department (Meltzer and Helman, 2021). Liu et al. (2020d) identified highly expressed circCRIM1 and proved that knockdown of circCRIM1 suppressed the growth and metastasis of osteosarcoma, activating autophagy at the same time. The miR-432-5p/HDAC4 axis has been shown to mediate the oncogenic roles of circCRIM1. Zhang et al. (2020b) found that H₂O₂ refrained the progression of osteosarcoma, while upregulating the circKMT2D in osteosarcoma. Following explorations demonstrated that silencing circKMT2D markedly impaired the viability and metastasis of osteosarcoma, while activating the autophagy process and strengthening the anti-cancer effect of H₂O₂.

Although chemotherapies and stem cell transplantation targeting malignant hematological diseases, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and multiple myeloma (MM), have achieved significant progress in recent years, the prognosis of hematological cancers remains unsatisfactory (Carella et al., 2018; Szalat and Munshi, 2019; Stanchina et al., 2020).

In AML cells, researchers observed high expression of circ_0009910, knockdown of which could remarkably restrain their proliferation, sphere formation, and autophagy. Furthermore, evidence indicated that circ_0009910 directly bound miR-491-5p through a sponging mechanism, finally targeting gene B4GALT5 which alleviated the effects of upregulated miR-491-5p on cell proliferation (Wu et al., 2021). The same circ_0009910/miR-34a-5p sponge system also modulated ULK1-induced autophagy in imatinib-resistant CML cells (Cao et al., 2020). Another signaling axis was found in doxorubicin (ADM)-resistant AML cells. Over-expression of circPAN3 induced more autophagic activities through the AMPK/mTOR pathway, a well-known molecular signaling axis involved in autophagy (Altman et al., 2014; Shang et al., 2019), hence promoting the resistance of AML. With the silence of circPAN3, the autophagic activities were significantly downregulated and so was the drug resistance (Shang et al., 2019). These studies not only confirmed the close relationship between circRNAs and autophagy but also provided novel targets for drug-resistant leukemias. Moreover, downregulation of has_circ_0003489 was reported to alter the death pattern of MM cells in vitro from autophagy to apoptosis and inhibit their viability and cell proliferation ability through acting as a sponge of miR-874-3p, which targeted HDAC1. The circ_0003489/miR-874-3p/HDAC1 axis played an essential role in modulating the balance between autophagy and apoptosis in MM cells, providing a novel therapeutic strategy for MM (Tian et al., 2021).

The HNCs we discussed in this review included oral squamous cell carcinoma (OSCC) (Gao et al., 2019b; Cui et al., 2021a; Zhang et al., 2021e; Gao et al., 2022), laryngeal carcinoma (Gao et al., 2020), and thyroid carcinoma (Liu et al., 2018), in which circRNA–autophagy axis also played essential roles. Sponging-specific miRNAs are the mainstream regulative mechanisms, which could be found in Supplementary Table S1.