Abstract
Hepatocellular carcinoma (HCC) is among the utmost deadly human malignancies. This type of cancer has been associated with several environmental, viral, and lifestyle risk factors. Among the epigenetic factors which contribute in the pathogenesis of HCC is dysregulation of long non-coding RNAs (lncRNAs). These transcripts modulate expression of several tumor suppressor genes and oncogenes and alter the activity of cancer-related signaling axes. Several lncRNAs such as NEAT1, MALAT1, ANRIL, and SNHG1 have been up-regulated in HCC samples. On the other hand, a number of so-called tumor suppressor lncRNAs namely CASS2 and MEG3 are down-regulated in HCC. The interaction between lncRNAs and miRNAs regulate expression of a number of mRNA coding genes which are involved in the pathogenesis of HCC. H19/miR-15b/CDC42, H19/miR-326/TWIST1, NEAT1/miR-485/STAT3, MALAT1/miR-124-3p/Slug, MALAT1/miR-195/EGFR, MALAT1/miR-22/SNAI1, and ANRIL/miR-144/PBX3 axes are among functional axes in the pathobiology of HCC. Some genetic polymorphisms within non-coding regions of the genome have been associated with risk of HCC in certain populations. In the current paper, we describe the recent finding about the impact of lncRNAs in HCC.
Introduction
Liver cancer is among the most lethal malignancies among both sexes. More than 8% of cancer-related mortalities are due to this type of cancer (). Hepatocellular carcinoma (HCC) includes more than 75% of the primary liver neoplasms (). Several factors have been related with elevated risk of HCC among them are chronic infection with hepatitis B virus (HBV) B or hepatitis C virus (HCV), dietary exposure with aflatoxin, excessive alcohol use, obesity, and smoking (). The cirrhosis-induced carcinogenic alterations have been detected in 90% of HCC patients (). High throughput sequencing methods have shown the occurrence of several genetic changes in the HCC samples () among the early events are inactivating mutations in insulin-like growth factor 2 receptor (). Catenin Beta 1 (CTNNB1) and Tumor Protein P53 (TP53) are the utmost recurrently mutated oncogene and tumor suppressor gene in HCC, respectively (). In addition to these somatic mutations, several epigenetic factors partake in the evolution of HCC. Such involvement is further highlighted by the fact that liver is an organs that is continuously adapting to extremely various environmental factors (). Non-coding RNAs are among epigenetic elements that contribute in the pathogenesis of HCC. Long non-coding RNAs (lncRNAs) can affect expression of genes via diverse mechanisms including recruitment of regulatory protein complexes, acting as a decoy, changing genome organization and modulating the distribution of posttranslational modifications (). These transcripts have sizes longer than 200 nucleotides and are comparable with mRNAs in the terms of chromatin state of genome loci, their transcription by RNA polymerase II, polyadenylation, 5’ capping and being spliced, yet they do not produce large-sized polypeptides (). However, there are several reports demonstrating the presence of stable, functional micropeptides being translated from lncRNAs (). Several lines of evidence indicates that these transcripts contribute in the pathophysiology of HCC (). In the present manuscript, we review the current knowledge about the partake of lncRNAs in the pathogenesis of HCC.
Up-regulated lncRNAs in HCC
The LINC01138 is located in a frequently amplified region in HCC. This lncRNA transcript is stabilized by IGF2BP1/IGF2BP3. Over-expression of LINC01138 in HCC confers malignant characteristics and is associated with poor survival of patients. Mechanistically, this lncRNA interacts with arginine methyltransferase 5 and increases the stability of this protein through inhibiting ubiquitin-mediated degradation in proteasomes (). Over-expression of the lnc-Epidermal Growth Factor Receptor (EGFR) regulatory T cells (Tregs) has been related with tumor size and levels of EGFR/Foxp3. Its over-expression has also been negatively correlated with the levels of interferon (IFN)-γ in HCC patients and animal models. This lncRNA promotes Treg differentiation, inhibits function of cytotoxic T cells and increases HCC growth. These effects are exerted through binding of lnc-EGFR with EGFR, increasing its stability and activation of the AP-1/NF-AT1 axis (). The oncogenic lncRNA HULC has been shown to exert its effects via modulation of phosphorylation pattern of YB-1. Notably, up-regulation of this lncRNA in HCC has been correlated with pathological grade and patients’ outcome. HULC can also increase cell proliferation, migration, and invasion and suppress cisplatin-associated cell apoptosis (). LncRNA-MUF is another over-expressed lncRNA in HCC tissues whose up-regulation has been correlated with poor clinical outcome. This lncRNA has an indispensable impact in epithelial-mesenchymal transition (EMT). Such effects have been exerted through binding with Annexin A2 and induction of the Wnt/β-catenin signaling. Mechanistically, lncRNA-MUF serves as a competing endogenous RNA (ceRNA) for miR-34a, resulting in up-regulation of Snail1 induction of EMT process (). GHET1 over-expression in HCC sections has been associated with vascular invasion, cirrhosis, size of tumor, histological grade, and poor clinical outcome. GHET1 silencing has suppressed cell proliferation and prompted both cell cycle arrest and cell apoptosis. GHET1 can suppress expression of KLF2 in HCC cells through recruitment of PRC2 into its promoter (). MALAT1 is another up-regulated lncRNA in HCC, which affect neoplastic transformation through several mechanisms among them is its role as a ceRNA. Figure 1 depicts this mechanism in HCC.
Figure 1
Table 1
| lncRNA | Sample | Cell line | Interacting partners | Signaling pathway | Association with clinical features | Function | Reference |
|---|---|---|---|---|---|---|---|
| NEAT1 | 40 HCC tissues and paired ANTs, Male BALB/c nude mice | L02, 293 T, HepG2, Huh7, SK-Hep-1, HCCLM3 | miR-124-3p, ATGL | – | Patient survival | Promotes HCC cell growth through miR-124-3p-mediated downregulation of ATGL. | () |
| NEAT1 | 30 HCC tissues and paired ANTs, BALB/c athymic nude mice | HepG2, L02, Huh7, | miR-129-5p, VCP, IκB | – | – | Enhances proliferation of HCC cells via affecting miR-129-5p-VCP-IκB. | () |
| NEAT1 | – | Huh7, Hep3B, HepG2, Bel-7404, SK-Hep1, LO2, HEK-293T | miR-485, STAT3 | – | – | Contributes to evolution of HCC through sequestering miR-485 and upregulation of STAT3. | () |
| NEAT1 | 86 HCC tissues and paired ANTs | SMMC-7721, Huh-7, Hep3B, THLE-2 | – | – | Patient survival, liver cirrhosis, microvascular invasion, TNM stage | Promotes proliferation HCC cells | () |
| NEAT1 | 62 HCC tissues and paired ANTs | MHCC97H, MHCC97L, SMCC7721, Huh7, LO2 | miR-613 | – | tumor size, vascular invasion | Stimulates proliferation and invasion via regulating miR-613 | () |
| NEAT1 | 12 female BALB/c, nude mice | Hep3B, LM3, MHCC97L, SK-hep1, HepG2, LO2, HEK-293T | hsa-miR-139-5p, TGF-β1 | – | – | Promotes HCC progression via sequestering hsa-miR-139-5p and upregulation of TGF-β1 | () |
| NEAT1_2 | 21 HCC tissues and paired ANTs | LO2, Huh7, SMMC-7721, PLC5, Bel-7402 | miR-101-3p, WEE1 | – | – | Reduces radiosensitivity through miR-101-3p- WEE1 axis | () |
| PTTG3P | 46 HCC tissues and paired ANTs, 90 paraffin-embedded tissues and ANTs, male BALB/C nude mice | HepG2, Hep3B | PTTG1 | PI3K/AKT signaling pathway | Patient survival, tumor size, TNM stage | Stimulates proliferation, migration and invasion and blocks apoptosis via upregulating PTTG1 | () |
| PTTG3P | 50 HCC tissues and paired ANTs, female nude mice | HepG2, Hep3B, Huh-7, HLF, SK-HeP-1, SNU-449, LO2 | CCND1, PARP2, miR-383 | PI3K/AKT | tumor size, tumor stage, metastasis | Promotes proliferation, migration, and invasion and inhibits apoptosis in HCC cells. | () |
| UBE2CP3 | 46 HCC tissues and ANTs, male BALB/c nude mice | HepG2, SMMC-7721, HUVEC | – | ERK/HIF-1α/p70S6K/VEGFA signaling | Patient survival, tumor invasion, tumor number | Promotes migration, invasion, and angiogenesis through activating ERK/HIF-1α/p70S6K/VEGFA signaling | () |
| LINC00461 | 87 HCC tissues and paired ANTs, mice | Huh7, SMMC-7721, MHCC97H, Hep3B, HepG2, LO2 | miR-149-5p, LRIG2 | – | Advanced stage, metastasis | Promotes proliferation, migration, and invasiveness via miR-149-5p- LRIG2 axis | () |
| MALAT1 | 20 HCC tissues and paired ANTs, female Nude mice | LO2 cells, HepG2 cells, Huh-7 cells, THP-1, HUVEC | miR-140, VEGF-A | – | – | Promotes angiogenesis of HCC cells through targeting miR-140 and surging VEGF-A | () |
| MALAT1 | 20 HCC tissues and paired ANTs | LO2, Bel7404, Huh7, HepG2 | miR-204, SIRT1 | – | – | Promotes migration and invasion of HCC cells through sponging miR-204 and surging SIRT1 | () |
| MALAT1 | 56 HCC tissues and paired ANTs | Huh-6, HepG2, SMMC-7721, Bel-7402, LO2 | miR-143-3p, ZEB1 | – | Patient survival, TNM stage, distant metastasis | Promotes HCC development via sequestering miR-143-3p and regulation of ZEB1 | () |
| MALAT1 | 30 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, Huh7, HEK-293T | miR-30a-5p, Vimentin | – | – | Promotes migration and invasion in HCC cells via affecting miR-30a-5p/Vimentin axis | () |
| MALAT1 | – | Huh7, SNU-423, PLC, Hep3B | miR-200a | – | – | Regulates proliferation, migration, and invasion under hypoxic condition through sponging miR-200a. | () |
| MALAT1 | 15 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, HuH7, HEK293T | miR-124-3p, Slug | – | Patient survival, tumor size, MVI, differentiation status | Promotes migration and invasion of HCC cells through influencing miR-124-3p/Slug axis | () |
| MALAT1 | – | L-02, QSG-7701, HepG2, MHCC97 | miR-195, EGFR | PI3K/AKT and JAK/STAT signaling pathways | – | Promotes growth and motility of HCC cells through regulation of miR-195/EGFR axis | () |
| MALAT1 | 30 HCC tissues and paired ANTs, female BALB/c nude mice | HepG2, Hep3B, HuH7, PLC/PRF5 | miR-22, SNAI1 | – | – | Contributes to HCC progression though sponging miR-22 and upregulation of SNAI1 expression | () |
| MNX1-AS1 | 81 HCC tissues and paired ANTs, mice | Huh7, SMMC-7721, MHCC97H, Hep3B, HepG2, and LO2 | miR-218-5p, COMMD8 | – | Patient survival, TNM stage, metastasis | Enhances proliferation and invasion of HCC cells through targeting miR-218-5p and inhibition of COMMD8 | (37) |
| MCM3AP-AS1 | 80 HCC tissues and paired ANTs, male BALB/c nude mice | LO2, HepG2, Hep3B, Huh7, SMMC-7721 | miR-194-5p, FOXA1 | – | Poor prognosis, tumor size, tumor grade, advanced tumor stage | Promotes proliferation, colony formation, and cell cycle transition and decreases apoptosis in HCC cells | () |
| MCM3AP-AS1 | 25 HCC tissues and paired ANTs | HepG2, Huh-7, 293T | miR-455 | – | Patient survival | Promotes HCC metastasis through interacting with and regulation of EGFR expression | () |
| TUG1 | 77 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, MHCC-97H, Hep3B, L02 | KLF2 | – | tumor size, BCLC stage | Promotes HCC cells proliferation through epigenetically repression of KLF2 | () |
| TUG1 | HCC tissues and paired ANTs | – | miR-455-3p, AMPKβ2 | – | Patient survival | Affects cell growth, metastasis, and glycolysis via miR-455-3p/AMPKβ2 axis | () |
| TUG1 | 92 HCC tissues and paired ANTs, female BALB/c athymic nude mice | HepG2, Hep3B, SMMC-7721, HCCLM3, Bel-7402 | miR-142-3p, ZEB1 | – | – | Contributes to metastasis and EMT process in HCC through downregulation of miR-142-3 and regulation of ZEB expression | () |
| TUG1 | 41 HCC tissues and paired ANTs, female BALB/C athymic nude mice | Hep3B, Huh7, Bel7402, HepG2, SMMC-7721, HL7702 | miR-144 | JAK2/STAT3 signaling pathway | – | Promotes proliferation, migration, and tumorigenesis via interacting with miR-144 | () |
| THOR | 80 HCC tissues and paired ANTs, nude mice | HCCLM3, SMMC7721 | – | PTEN/AKT signaling pathway | Patient survival | Enhances proliferation and metastasis of HCC cells by amplifying PTEN/AKT signaling | (44) |
| ANRIL | FFPE specimens of 43 pairs of HCC tissues and ANTs, male athymic BALB/c nude mice | Huh7, SMMC7721, HepG2, Hep3B, L02 | miR-199a-5p, ARL2 | – | – | Enhances mitochondrial function in HCC cells through regulation of miR-199a-5p/ARL2 axis | (45) |
| ANRIL | – | HepG2 | miR-191 | – | – | Promotes proliferation, migration, and invasion and reduces apoptosis in HCC cells through downregulation of miR-191 | (46) |
| ANRIL | 77 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, Hep3B, MHCC-97H | KLF2 | – | tumor size, BCLC stage | Promotes proliferation, invasion, and reduces apoptosis in HCC cells | (47) |
| ANRIL | 31 HCC tissues and paired ANTs, female BALB/C athymic nude mice | SMMC772, HUH7, Hep3B, HepG2 | miR-122-5p | – | – | Promotes proliferation, metastasis and invasion of HCC cells via affecting miR-122-5p expression | (48) |
| ANRIL | 130 tissues and paired ANTs | HepG2 | – | – | Patient survival, histologic grade, TNM stage | Promotes proliferation, migration, and invasion of HCC cell. | (49) |
| ANRIL | – | MHCC97, Li-7, THLE-3 | miR-144, PBX3 | PI3K/AKT and JAK/STAT signaling pathways | – | Surges proliferation, migration, and invasion of HCC cells through sponging miR-144 and upregulation of PBX3 | (50) |
| AWPPH | 88 HCC tissues and paired ANT, male athymic BALB/c nude mice | QSG-7701, SMMC-7721, HCCLM3, Huh7, HepG2 | YBX1, SNAIL1, PIK3CA | PI3K/AKT signaling pathway | Patient survival, encapsulation incomplete, microvascular invasion, TNM stage, BCLC stage | Promotes proliferation and migration of HCC cells through YBX1-mediated activation of SNAIL1 translation and PIK3CA transcription | (51) |
| PVT1 | 47 HCC tissues and paired ANTs, nude BALB/c male mice | L-02, SK-HEP-1, Hep G2, SMMC-7721, BEL-7402, Hep3B2.1-7, QGY-7703X4 | miR-150, HIG2 | – | – | Promotes proliferation, migration and invasion, and induced cell apoptosis in HCC cells through regulation of miR-150/HIG2 axis | (52) |
| PVT1 | 48 HCC tissues and paired ANTs | HepG2, Hep3B, Huh-7, HCCLM9, SK-Hep1, SMMC-7721 | miR-186-5p, YAP1 | – | Patient survival, vascular invasion, liver cirrhosis, TNM stage | Promotes proliferation, migration, and invasion through targeting miR-186-5p and enhancement of YAP1 | (53) |
| PVT1 | 80 HCC tissues and paired ANTs | Bel-7402, Huh7, Hep3B, HepG2 | miR-365, ATG3 | TNM stage, tumor size | Promotes autophagy in HCC cells via sponging miR-365 and upregulation of ATG3 | (54) | |
| SNHG1 | Male BALB/c nude mice | HL-7702, s Li-7, HuH7, HHCC, H-97, Hep3b, SMMC-7721 | miR-195-5p, PDCD4 | – | – | Promotes proliferation and migration of HCC cells through targeting miR-195-5p and upregulation of PDCD4 | (55) |
| SNHG1 | 82 HCC tissues and paired ANTs | SMMC-7721, MHCC97H, HCCLM3, HepG2, QSG-7701, L02 | p53 | – | Patient survival, tumor size, tumor differentiation, BCLC stage | Stimulates proliferation, cell cycle progression, and blocks apoptosis in HCC cells via inhibiting p53 | (56) |
| SNHG1 | 122 HCC tissues and paired ANTs | HepG2 | miR-195 | – | tumor size, TNM stage | Stimulates proliferation, migration, and invasiveness of HCC cells through inhibiting miR-195 | (57) |
| ENST00000429227.1 | 161 HCC tissues and paired ANTs | U937 | – | – | Patient survival, surgical margin, AFP, BCLC stage | Is associated with poor prognosis in HCC | (58) |
| H19 | 42 HCC tissues and paired ANTs | Huh 7 | – | MAPK/ERK signaling pathway | – | Its downregulation induces oxidative stress and reduces chemotherapy resistance of HCC cells. | (59) |
| H19 | 46 HCC tissues and paired ANTs | linesHepG2, SMMC-7721, Bel-7402, Huh-7 | miR-15b, CDC42 | CDC42/PAK1 pathway | – | Promotes proliferation, migration, and invasion and reduces apoptosis in HCC cells through regulating miR-15b/CDC42 axis. | (60) |
| H19 | – | HepG2, MHCC-97L, SK-hep1, Hun7, SMCC-7721, LO2, HEK- 293T | miR-326, TWIST1 | – | – | Promotes proliferation, migration, and invasion of HCC cells through regulating miR-326/TWIST1 axis. | (61) |
| HCG11 | 20 HCC tissues and paired ANTs | L-02, Huh7, HepG2, SMMC-7721, SK-HEP-1 | IGF2BP1 | MAPK signaling pathway | – | Promotes proliferation, migration, and invasion and reduces apoptosis in HCC cells | (62) |
| LINC00665 | 76 HCC tissues and paired ANTs, 24 female BALB/c nude mice | Huh-7, HepG2, HCCLM6, MHCC-97H, Hep3B, HL-7702 | miR-186-5p, MAP4K3 | – | Patient survival, tumor size, Edmondson grade | Enhances cell viability and decreases apoptosis and autophagy through regulation of miR-186-5p/MAP4K3 axis | (63) |
| CRNDE | 46 HCC tissues and paired ANTs | HepG2, Huh-7, HCCLM3, SNU449, SNU475, HepaRG, HL‐7702 | miR-217, MAPK1 | – | AJCC stage, vascular invasion, distant metastasis | Promotes proliferation, migration and invasion in HCC cells via affecting miR-217/MAPK1 axis | (64) |
| CRNDE | 23 HCC tissues and paired ANTs, BALB/c (nu/nu) mice | QSG-7701, HepG2, Hep3B, Huh7 | – | PI3K/Akt and Wnt/β-catenin signaling pathways | Patient survival | Promotes proliferation of HCC cells through regulation of mentioned signaling pathways | (65) |
| CRNDE | 12 HCC tissues and paired ANTs, male BALB/c nude mice | SMMC7721, SK-hep1, Huh7, HepG2 | miR-136-5P, IRX5 | Affects proliferation, migration, and invasiveness of HCC cells via targeting miR-136-5P and regulation of IRX5 | (66) | ||
| CRNDE | 25 HCC tissues and paired ANTs, 10 female athymic BALB/c nude mice | HepG2, Huh7, L-02 | miR-203, BCAT1 | – | – | Affects proliferation, migration, and invasiveness of HCC cells by regulating miR-203/BCAT1 axis | (67) |
| CRNDE | 60 HCC tissues and paired ANTs, male athymic BALB/c nude mice | HL7702, MHCC97H, HCCLM6, SNU-398, Huh7 | miR-337-3p, SIX1 | – | – | Promotes HCC progression through sponging miR-337-3p and upregulation of SIX1 | (68) |
| FOXD2-AS1 | 18 HCC tissues and paired ANTs | L-02, HepG2, Huh-7, SMMC-7721, Bel-7402, Hep3B | miR-185, AKT | – | – | Supports proliferation and metastasis of HCC cells through regulation of miR-185/AKT axis | (69) |
| FOXD2-AS1 | 88 HCC tissues and paired ANTs | L-02, HepG2, Hep3B, SMMC-7721, LM3 | DKK1 | Wnt/β-catenin signaling pathway | Patient survival | Contributes to progression of HCC by epigenetically silencing DKK1 and activation of Wnt/β-catenin signaling pathway | (70) |
| LINC00488 | 46 HCC tissues and paired ANTs, 30 nude mice | L02, Huh-7, Hep3B, HCCLM3, MHCC97 | miR-330-5p, TLN1 | – | – | Promotes proliferation and angiogenesis of HCC cells through miR-330-5p-mediated upregulation of TLN1 | (71) |
| AY927503 | 57 HCC tissues and paired ANTs, female BALB/c nude mice | Hep3B, HepG2, SK-Hep1, LM3, BEL-7404, SMMC-7721, LO2, HUVEC, HEK-293T | ITGAV | – | Patient survival | Enhances cell migration, drug resistance, and metastasis in HCC cells through activation of ITGAV transcription | (72) |
| lncRNA-PE | 24 HCC tissues and paired ANTs | BEL-7402, SK-Hep-1, LO2 | miR-200a/b, ZEB1 | – | – | Enhances migration, invasion and EMT process in HCC cells through miR-200a/b/ZEB1 axis | (73) |
| HULC | 30 HCC tissues and paired ANTs | HepG2, SMMC7721, LO2 | miR-372-3p, Rab11a | – | TNM stage | Promotes proliferation and invasion and suppresses apoptosis through sponging miR-372-3p and upregulation of Rab11a | (74) |
| HULC | male athymic Balb/C mice | Hep3B | miR-15a, P62, PTEN | AKT-PI3K-mTOR signaling pathway | – | Contributes to HCC progression through regulation of miR-15a, P62 and PTEN | (75) |
| HULC | 41 HCC tissues and paired ANTs | HepG2, SMMC-7721 | YB-1 | – | Patient survival, differentiation | Promotes proliferation, migration and invasion and suppresses cisplatin-induced apoptosis in HCC cells | (76) |
| SBF2-AS1 | 18 male Balb/c nude mice | HepG2, Hep3B, SUN475, BEL-7405, BEL7404, BEL-7402, THLE-3 | miR-140-5p, TGFBR1 | – | Patient survival, lymph node metastasis, histologic grade, TNM stage | Contributes to evolution of HCC via sponging miR-140-5p and upregulation of TGFBR1 | (77) |
| SBF2-AS1 | 134 HCC tissues and paired ANTs | HCCLM3, Huh7, SK-Hep1, HepG2, L02 | – | – | vein invasion, TNM stage | Affects proliferation, migration and invasion of HCC cells | (78) |
| UC001kfo | 82 HCC tissues and 20 ANTs, SPF BALB/c nude mice | GSG701, Hep3B, HepG2, Huh7, SMMC 7721, HCC LM3, L02 | α-SMA | – | Patient survival, macro-vascular invasion, TNM stage | Affects proliferation, metastasis and EMT process through targeting α-SMA | (79) |
| HOTTIP | 20 HCC tissues and 20 ANTs, male BALB/C nude mice | BEL7402, MHCC97H | miR-125b, HOXA | – | – | Promotes proliferation, migration, and tumorigenesis of HCC cells. | (80) |
| FOXD2-AS1 | 140 HCC tissues and paired ANTs, 12 female BALB/c nude mice | Hep3B, MHCC97-L, MHCC97-H, SK-HEP1, HCCLM3, HL7702 | miR−206, ANXA2 | – | Patient survival | Increases cell viability and metastasis of HCC cells through miR−206/ANXA2 axis | (81) |
| LUCAT1 | 90 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, SMMC-7721, SNU‐423, Hep3B, Huh7, MHCC‐97H, L02 | – | – | Patient survival, tumor size, metastasis, TNM stage | Affects proliferation and metastasis of HCC cells through inhibition of phosphorylation of ANXA2 | (82) |
| AK001796 | 73 HCC tissues and paired ANTs | LO2, g SMMC-7721, Huh-7, MHCC-97H, MHCC-97L | – | – | Patient survival, tumor size, TNM stage | Promotes proliferation and invasion of HCC cells | (83) |
| FEZF1-AS1 | 139 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, SK-hep1, Huh7, HCCLM3, LO2 | – | JAK2/STAT3 signaling pathway | Patient survival, tumor size, TNM stage, venous invasion | Promotes proliferation, migration and invasion of HCC cells | (84) |
| MINCR | 161 HCC tissues and paired ANTs | – | – | – | Patient survival, TNM stage, histological grade | Contributes to progressive clinicopathological features and poor survival | (85) |
| MINCR | 70 primary HCC tissues and paired ANTs | SMMC-7721, Huh7, HCC-LM3, HepG2, MHCC-97H, HL-7702 | – | – | – | Promotes proliferation, migration, and invasion. | (86) |
| LINC01152 | 30 pairs of HBV-HCC related tissues and HCC tissues, nude mice | Huh7, HepG2, Hep3B | IL-23 | – | – | Enhances proliferation, survival and tumor formation ability through IL-23 | (87) |
| XIST | 88 HCC tissues and paired ANTs, male BALB/c-nu/nu mice | LM9, Hh7, Hep3B, HepG2, LO2 | miR-139-5p, PDK1 | AKT signaling pathway | Patient survival, tumor size | Promotes cell proliferation and reduces apoptosis through regulation of miR-139-5p/PDK1/AKT axis | (88) |
| XIST | 52 HCC tissues and paired ANTs | MHCC97L, MHCC97H, HepG2, SMMC7221, Huh7, Bel-7402, HL-7702 | miR-194-5p, MAPK1 | – | Patient survival, tumor size, vascular invasion | Promotes proliferation, migration and invasion of HCC cells through sponging miR-194-5p and regulation of MAPK1 expression | (89) |
| TRPM2-AS | 108 HCC tissues and paired ANTs | HCCLM3, Huh7, SMMC-7721, SKHep1, HepG2, QSG7701 | Patient survival, tumor size, AJCC stage, tumor differentiation | Promotes proliferation and reduces apoptosis in HCC cells | (90) | ||
| LINC-ITGB1 | 56 HCC tissues and paired ANTs, blood samples from 80 HCC patients and 44 healthy controls | C3A, HEP G2, m, THLE-3 | ROCK1 | – | – | Promotes proliferation, migration and invasion of HCC cells through upregulation of ROCK1 | (91) |
| LSINCT5 | 126 HCC tissues and paired ANTs, female nude mice | 97L, HepG2, Hep3B, 7721, and Huh7, 293T, L02 | miR-4516, HMGA2 | – | Patient survival, TNM stage, tumor size, metastasis | Promotes HCC progression through regulation of miR-4516/HMGA2 axis | (92) |
| XLOC | 68 HCC tissues and paired ANTs | HepG2, Hep3B, SMMC-7721, Bel-7402 | – | – | Patient survival, vascular invasion tumor size, Edmindson grade | Promotes proliferation and migration and reduces apoptosis in HCC cells | (93) |
| HNF1A-AS1 | – | SMMC-7721, Huh7, MHCC97L, HepG2, LO2 | NKD1, p21 | – | – | Promotes proliferation of HCC cells through inhibition of NKD1 and p21 via interacting with EZH2 | (94) |
| HNF1A-AS1 | 40 HCC tissues and paired ANTs | HepG2, SMMC-7721, PLC/PRF/5, Huh7, HL7702 | hsa-miR-30b-5p, ATG5 | – | tumor size, multiplicity of tumors, histological differentiation, TNM stage | Reduces apoptosis rate and promotes autophagy in HCC cells through sponging hsa-miR-30b-5p | (95) |
| URHC | 52 HCC tissues and paired ANTs | HepG2, SMMC7721, Huh7, HL-7702 | ZAK | ERK/MAPK signaling pathway | Patient survival, tumor size, tumor number | Promotes cell proliferation and inhibits apoptosis through suppression of ZAK | (96) |
| UCA1 | 60 HCC tissues and paired ANTs, male BALB/C nude mice | LO2, MHCC97L, Huh7, MHCC97H, SK-hep1 | miR-203, Snail2 | – | tumor size, vascular invasion, AJCC stage | Promotes HCC progression through targeting miR-203 and upregulation of Snail2 | (97) |
| AK021443 | 20 HCC tissues and paired ANTs, male BALB/c-nu/nu mice | Bel-7402, Sk-Hep1, HepG2, Huh-7, Bel-7404, LO2 | – | – | – | Promotes proliferation, migration, invasion and colony formation in HCC cells | (98) |
| RUSC1-AS-N | 66 HCC tissues and paired ANTs | QSG-7701, SMMC-7721, HCCLM3, Huh7 | – | – | Patient survival, tumor size, vein invasion, encapsulation, BCLC stage | Promotes cell viability and reduces apoptosis and cell cycle arrest | (99) |
| CCAT1 | 40 HCC tissues and paired ANTs | MHCC97H, MHCC97L, Hep3B, SMCC-7721, LO2 | miR-490-3p, CDK1 | – | tumor site, AJCC stage | Promotes proliferation and invasion of HCC cells through targeting miR-490-3p and regulation of CDK1 | (100) |
| CCAT1 | 66 HCC tissues and paired ANTs | LO2 and QSG-7701, SMMC-7721, Hep3B, Huh7, HepG2 | let-7, HMGA2, c-Myc | – | Patient survival, tumor size, microvascular invasion, AFP | Enhances proliferation and migration of HCC cells through sponging let-7 and regulation of HMGA2 and c-Myc expression | (101) |
| CCAT1 | 39 HCC tissues and paired ANTs | HCCLM3, Huh7, Hep3B, HepG2, L02 | miR-181a-5p, ATG7 | – | – | Promotes autophagy and proliferation in HCC cells through sponging miR-181a-5p and regulation of ATG7 expression | (102) |
| CCAT1 | 65 HCC tissues and 35 normal liver samples | Hep3B | miR-30c-2-3p, CCNE1 | – | metastasis | Promotes HCC cells proliferation by sequestering miR-30c-2-3p and upregulation of CCNE1 | (103) |
| CCAT2 | 20 HCC tissues and paired ANTs, male BALB/c-nude mice | SMMC7721, SK-hep1, HepG2, Huh7, L02 | NDRG1 | – | Stimulates proliferation and metastasis of HCC cells through upregulation of NDRG1 | (104) | |
| SNHG16 | 71 HCC tissues and paired ANTs | HL-7702, SK-Hep-1, Huh7, Hep3B, HepG2 | – | – | Patient survival, tumor size, AFP level, PVTT, metastasis | Promotes proliferation, migration and invasion and increases sorafenib resistance in HCC cells | (105) |
| SNHG16 | 40 HCC tissues and paired ANTs, BALB/c nude mice | HepG2, SMMC7721, Hep3B, Bel7402, Huh7, LO2 | miR-195 | – | TNM stage, metastasis | Enhances proliferation, invasion and tumorigenesis of HCC cells through targeting miR-195 | (106) |
| SNHG10 | 64 HCC tissues and paired ANTs | SNU-182, Huh-7, Hep3B, SK-Hep1, and SNU-387, HEK293T, HCCLM3 | miR-150-5p, SCARNA13 | – | Patient survival | Contributes to HCC progression and metastasis through modulating SCARNA13 | (107) |
| SNHG12 | 48 HCC tissues and paired ANTs | SK-Hep1 | miR-199a/b-5p, MLK3 | NF-κB signaling pathway | Patient survival, tumor size, vascular invasion, TNM stage | Enhances tumorigenesis and metastasis of HCC cells via targeting miR-199a/b-5p | (108) |
| SNHG20 | 96 HCC tissues and paired ANTs | LO2, MHCC97L, SMCC7721, MHCC97H, Huh-7 | EZH2, E-cadhein | – | Patient survival, tumor size, TNM stage | Promotes proliferation and invasion of HCC cells through binding to EZH2 and regulation of E-cadherin expression | (109) |
| SNHG5 | 48 HCC tissues and paired ANTs | Hep3B, HepG2, SMCC-7721, MHCC-97L, MHCC-97H, Huh7, LO2 | miR-26a-5p, GSK3β | Wnt/β-catenin signaling pathway | Patient survival, tumor size, HBV infection, histologic grade, TNM stage | Promotes HCC progression and metastasis through targeting miR-26a-5p and regulation of GSK3β | (110) |
| SNHG6 | Expression data of HCC obtained from TCGA and GEO | MHCC-97H, HCC-LM3 | let-7c-5p, c-Myc | – | Patient survival | Enhances proliferation of HCC cells through sponging let-7c-5p and upregulation of c-Myc | (111) |
| SNHG6 | 12 HCC tissues and paired ANTs, female BALB/c mice | HL-7702, HepG2, Hep3b, HLE, Huh-7 | miR-139-5p, SERPINH1 | – | – | Promotes HCC progression via targeting miR-139-5p and regulation of SERPINH1 | (112) |
| SNHG6-003 | 52 HCC tissues and paired ANTs, FFPE tissues from 160 patients | BEL-7402, SMMC-7721, MHCC-97H, SK-Hep-1, Huh7, HCC-LM3 | miR-26a/b, TAK1 | – | Patient survival, portal vein tumor thrombus, Barcelona Clinic Liver Cancer stage, distant metastasis | Promotes HCC cells proliferation and drug resistance by sponging miR-26a/b and upregulation of TAK1 | (113) |
| SNHG7 | 40 HCC tissues and paired ANTs, male BALB/c nude mice | HepG2, HCC-LM3 | miR-425 | Wnt/β-catenin/EMT signaling pathway | Patient survival | Enhances proliferation, migration and invasiveness via sponging miR-425 and regulation of Wnt/β-catenin/EMT signaling pathway | (114) |
| SNHG7 | 80 HCC tissues and paired ANTs, BALB/C nude mice | LO2, Hhu7, Hep3B, HCCLM3, MHCC97H | miR-122-5p, RPL4 | – | Patient survival, tumor stages, tumor grades, vascular invasion | Promotes proliferation, migration and invasiveness via affecting miR-122-5p and RPL4 | (115) |
| SNHG8 | 23 HCC tissues and paired ANTs, female immune-deficient nude mice | LO2, Huh6, Huh7, SK-hep1, HepG2, PLC5 | miR-149 | – | Recurrence | Promotes Tumorigenesis and metastasis through sponging miR-149 | (116) |
| SNHG15 | 101 HCC tissues and paired ANTs | HuH-1, HuH-7, L-O2 | miR-490-3p, HDAC2 | – | Tumor size, Edmondson-Steiner grading, TNM stage | Promotes proliferation, migration and invasion via regulating miR-490-3p/HDAC2 axis | (117) |
| CCAL | 37 HCC tissues and ANTs, 60 male nude mice | Huh7, HCCLM3, LO2 | AP-2α | Wnt/β-catenin signaling pathway | tumor metastasis, TNM stage | Promotes proliferation and invasion of HCC cells through upregulation of AP-2α | (118) |
| Sox2ot | 84 HCC tissues and ANTs | HepG2, SMMC-7721 | – | – | Patient survival, histological grade, TNM stage, vein invasion | Promotes HCC cells metastasis | (119) |
| SPRY4-IT1 | male nude mice | MHCC97H, MHCC97L, SKhep-1, LO2 | E-cadherin | – | – | Stimulates proliferation and invasion of HCC cells via interaction with EZH2 and repression of E-cadherin levels | (120) |
| SPRY4-IT1 | 82 HCC tissues and paired ANTs | HL7702, MHCC97L, MHCC97H, HepG2, SMMC7721 | ERRα | – | Patient survival, TNM stage, metastasis | Promotes proliferation, migration and invasion and decreases apoptosis via suppressing ERRα expression | (121) |
| PANDAR | 482 HCC tissues and paired ANTs | HCCLM3, Hep3B, HepG2, Huh-7, MHCC97H, PLC, SMMC-7402, SMMC-7721 | – | – | Patient survival, liver cirrhosis, HBs Ag, AFP, tumor nodule, vascular invasion, TNM stage | Promotes HCC tumorigenesis and is associated with poor prognosis | (122) |
| linc-ROR | female BALB/c nude mice | HepG2, SMMC-7721 | miR-145, RAD18 | – | – | Promotes metastasis, EMT process and radioresistant in HCC cells through targeting miR-145 and regulation of RAD18 expression | (123) |
| CARLo-5 | 97 HCC tissues and paired ANTs | HepG2, Hep3B, SK-HEP1, SMMC7721, MHCC97-L, MHCC97-H, PLC/PRF/5, HCCLM3 | – | – | Patient survival, liver cirrhosis, tumor number, vascular invasion, capsular formation, Edmondson-Steiner grade | Promotes proliferation, migration and invasion of HCC cells | (124) |
| AB019562 | 50 HCC tissues and paired ANTs | SMMC-7721, PLC/PRF/5, C3AHCC, THLE-3, HepG2 | – | – | – | Promotes proliferation, migration and invasive features and reduces apoptosis in HCC cells | (125) |
| PlncRNA-1 | 84 HCC tissues and paired ANTs, male BALB/c nu/nu mice | HCCLM3, Huh7, SK-Hep1, HepG2, L02 | – | – | Patient survival, tumor size, vascular invasion, TNM stage | Promotes metastasis and EMT process in HCC cells and is correlated with poor prognosis | (126) |
| lncRNA-TPTE2P1 | 72 HCC tissues and 66 normal tissues, | HepG2, Huh7, MHCC97, Bel7402, SMMC7721, HCCLM3 | – | – | tumor size, distant metastasis, differentiation degree, TNM stage | Promotes proliferation, migration and EMT process of HCC cells | (127) |
| PCAT-1 | 82 HCC tissues and paired ANTs | HepG2, Bel-7402 | – | – | – | Increases proliferation and migration and inhibits apoptosis in HCC cells | (128) |
| PCAT-14 | 39 HCC tissues and paired ANTs | Huh7, HCCLM3, HepG2, SMMC7721, PLC5, QGY7701, LO2 | miR-372 | – | Patient survival, TNM stage, tumor metastasis, tumor size | Promotes proliferation and invasion of HCC cells through inducing methylation of miR-372 | (129) |
| BLACAT1 | 37 HCC tissues and paired ANTs, male athymic nude (nu/nu) mice | HeG2, MHCC97L, HuH7, Hep3B, SK-HEP-1, SNU-449, SNU-182, SNU-429, bel-7402, THLE2, THLE3 | has-miR-485-5p | – | – | Promotes proliferation and invasion in HCC cells via upregulation of has-miR-485-5p. | (130) |
| DLX6-AS1 | 60 HCC tissues and paired ANTs, 20 male BALB/c nude mice | MHCC97L, HCCLM3, HepG2, Hep3B, Huh7, LO2 | miR-203a, MMP-2 | – | tumor size, Edmondson grading, TNM stage | Contributes to HCC progression via regulating miR-203a/MMP-2 axis | (131) |
| RAB5IF | – | HepG2, Hep3B, Huh7, MCF-7, A549, HeLa | LGR5 | – | – | Promotes HCC progression via LGR5 mediated elevation of β-catenin and c-Myc | (132) |
| LOC90784 | 64 HCC tissues and paired ANTs | L02, HepG2, SMMC7721, Bel-7404, PLC/PRF/5 | – | – | Patient survival, tumor differentiation, TNM stage, venous invasion, HBV status, serum AFP | Promotes cell proliferation, migration and invasion and reduces apoptosis | (133) |
| HOTAIR | 53 HCC tissues and paired ANTs | HepG2, Bel-7402 | RBM38 | – | – | Enhances migration and invasion of HCC cells via regulating RBM38 | (134) |
| HOTAIR | 30 HCC tissues and paired ANTs, female BALB/c nude mice | HepG2, Huh7, Hep3B, SMMC7721, MHCC97H, MIHA | miR-122 | – | – | Promotes cell proliferation and reduces cell cycle arrest through upregulation of miR-122 | (135) |
| BZRAP1-AS1 | 49 HCC tissues and paired ANTs, 90 specific pathogen-free female nude mice | L-02, HuH-7, HCCLM3, LI7, BEL-7405, SK-HEP-1, BCLC-9 | THBS1 | – | tumor size, microvascular invasion, TNM stage | Promotes proliferation, migration and angiogenesis HCC cells through regulation of THBS1 | (136) |
| SNAI3-AS1 | 46 HCC tissues and paired ANTs | MHCC‐97L, MHCC‐97h, HepG2, Hep3B, Huh7, L02 | UPF1, Smad7 | TGF-β/Smad signaling pathway | Patient survival, tumor size, TNM stage | Promotes proliferation, metastasis and EMT process via regulation of UPF1 | (137) |
| TP73-AS1 | 84 HCC tissues and paired ANTs | HCCLM3, MHCC97L, SMMC7722, Hep3B,HepG2, THLE-3 | miR-200a, HMGB1, RAGE | – | Patient survival, tumor size, tumor nodule number, TNM stage | Promotes proliferation of HCC cells through regulation of miR-200a/HMGB1/RAGE axis | (138) |
| TP73-AS1 | 72 HCC tissues and paired ANTs, male BALB/c nude mice | HL-7702, human HCC cell line HepG2, Hep3B, SMCC-7721 | – | PTEN/Akt signaling pathway | – | Promotes cell proliferation and reduces apoptosis and radiosensitivity of HCC cells | (139) |
| HANR | 35 HCC tissues and paired ANTs, male nude mice | Hep3B, Huh-7, LO-2 | GSKIP, GSK3β | – | TNM stage, distant metastasis | Promotes cell growth, inhibits apoptosis and induces chemoresistance HCC | (140) |
| MIAT | 45 HCC tissues and paired ANTs, BALB/c nude mice | HepG2, Huh7, SK-HEP-1, HLE, L02 | miR-214 | – | – | Promotes proliferation and invasion of HCC cells through sequestering miR-214 | (141) |
| MIAT | 20 HCC tissues and paired ANTs | HepG2, SMMC-7721, PLC/PRF/5, Huh7, SK-hep-1, 293T | miR-22-3p, sirt1 | p53/p21 and p16/pRb signaling pathways | – | Its knockdown promotes cellular senescence and represses HCC tumorigenesis by regulating miR-22-3p/sirt1 axis | (142) |
| lncRNA FAL1 | 30 HCC tissues and paired ANTs | LO2, SMMC-7721, Huh7, HepG2, HepG2.2.15 | miR-1236 | – | Patient survival | Promotes proliferation and metastasis in HCC cells through targeting miR-1236 | (143) |
| CDKN2B-AS1 | 100 HCC tissues and paired ANTs, 24 BALB/c male nude mice | LO2, HepG2, Huh7, SMMC-7721 | let-7c-5p, NAP1L1 | PI3K/AKT/mTOR signaling pathway | Patient survival, tumor size, microvascular invasion, tumor grade, tumor stage | Promotes tumor growth and metastasis of HCC through targeting let-7c-5p and upregulation of NAP1L1 | (144) |
| CDKN2B-AS1 | 48 HCC tissues and paired ANTs | QGY-7703, PLC/ PRF/5, HB611, MHCC97 | – | – | Patient survival, tumor size, TNM stage | Promotes HCC cells proliferation and is associated with poor prognosis | (145) |
| CDKN2BAS | 85 HCC tissues and paired ANTs, nude mice | HCCLM3, SK-Hep-1, HUH7, MHCC97H, L02 | miR-153-5p, ARHGAP18 | MEK-ERK1/2 signaling pathway | – | Enhances proliferation and metastasis of HCC cells through sponging miR-153-5p and upregulation of ARHGAP18 | (146) |
| lncRNA-PDPK2P | 60 HCC tissues and paired ANTs, nude mice | MHCC97L, MHCC97H, BEL-7404, HCCLM3, SMMC7721 | PDK1 | PDK1/AKT/caspase 3 signaling pathway | Patient survival, tumor embolus, tumor differentiation | Promotes HCC progression through interaction with | (147) |
| lncRNA Ftx | 73 HCC tissues and paired ANTs | LO2, Huh7, SMMC-7721, Bel-7402 | – | – | – | Promotes proliferation, migration and invasion in HCC cells through PPARγ pathway | (148) |
| MIR4435-2HG | 64 HCC tissues and paired ANTs | SNU-398, SNU-182 | miRNA-487a | – | tumor size | Promotes proliferation of HCC cells through upregulation of miRNA-487 | (149) |
| SOX9-AS1 | 67 HCC tissues and paired ANTs, male BALB/C nude | Huh7, HepG2, HCCLM3, Hep3B, L02 | miR-5590-3p, SOX9 | Wnt/β-catenin | Patient survival | Contributes to tumor growth and metastasis through sponging miR-5590-3p and upregulation of SOX9 | (150) |
| SOX21-AS1 | 68 HCC tissues and paired ANTs | Hep3B, LM3, MHHC97H, HepG2, Huh7, LO2 | p21 | – | Patient survival, tumor size, Edminson Grade, vascular invasion, cirrhosis | Contributes to HCC progression through epigenetically silencing p21 by recruiting EZH2 to the promoter of p21 | (151) |
| HOXA11-AS | 66 HCC tissues and paired ANTs | HL-7702, HepG2, Hep3B, MHCC-97H, BEL7402 | miR-124 | – | Patient survival, tumor size, differentiation, TNM stage, lymph node metastasis, recurrence | Enhances migration and invasion of HCC cells through suppression of miR-124 by binding to EZH2 | (152) |
| HOXA-AS2 | 58 HCC tissues and paired ANTs, female BALB/c nude mice | MHCC97L, Huh7, HepG2, HCCLM3, SMMC-7721, MHCC97H, HL-7702 | miR-520c-3p, GPC3 | – | – | Promotes migration and invasion of HCC cells through sponging miR-520c-3p and upregulation of GPC3 | (153) |
| HOXB-AS3 | 36 HCC tissues and paired ANTs | HepG, PLC, Hep3B, LM3 | p53 | – | – | Its downregulation inhibits proliferation and induced apoptosis and cell cycle arrest in HCC cells through regulation of p53 | (154) |
| LINC00978 | 33 HCC tissues and paired ANTs, sera of 58 HCC patients, 49 liver benign disease patients and 45 healthy controls, 10 BALB/c nude mice | 7721, 7402, HepG2, LM3 | EZH2, p21, E-cadherin | – | – | Promotes proliferation, migration, and invasion through epigenetically silencing of p21 and E-cadherin | (155) |
| lncRNA-ATB | 72 HCC tissues and paired ANTs | SMMC-7721, HepG2 | YAP, ATG5 | – | Patient survival, tumor size, TNM stage | Promotes proliferation and clonogenicnity and also promotes autophagy by activating YAP and increasing ATG5 expression | (156) |
| NR2F1-AS1 | 47 HCC tissues from oxaliplatin-resistant and oxaliplatin‐sensitive, male nude mice | Huh7, HepG2, Lo-2 | miR-363, ABCC1 | – | – | Its knockdown suppresses migration, invasion and drug-resistant of HCC cells via regulating miR-363/ABCC1 axis | (157) |
| DANCR | Male athymic BALB/C nude mice | LO2, MHCC-97H, Huh7, HCC‐LM3, HepG2, MHCC‐97L, Hep3B, SMMC‐7721 | miR-27a-3p | ROCK1/LIMK1/COFILIN1 pathway | Patient survival, | Enhances proliferation and metastasis and regulates EMT process through targeting miR-27a-3p | (158) |
| DANCR | BALB/c mice | Hep3B, HepG2, Huh7, SNU449, SK‐hep‐1, LO2 | miR-216a-5p, KLF12 | – | – | Promotes HCC malignancy and progression through sponging miR-216a-5p and regulation of KLF12 expression | (159) |
| LINC00205 | 80 HCC tissues and paired ANTs | LO2, Hep3B, Huh7, HEK293T | miR-122-5p | – | Tumor size, venous infiltration, TNM stage | Enhances proliferation, migration and invasion in HCC cells via miR-122-5p | (160) |
| OSER1-AS1 | 34 HCC tissues and paired ANTs | HepG2, Hep3b | miR-372-3p, Rab23 | – | Patient survival, tumor size, tumor stages | Its knockdown suppresses cell proliferation, invasion and migration and induces apoptosis via miR-372-3p-mediated upregulation of Rab23 | (161) |
| DLEU2 | 50 HCC tissues and paired ANTs | SMMC7721, L02, Huh7, HCCLM3 | EZH2 | – | vascular invasion, tumor stage | Its knockdown represses proliferation, migration and invasion of HCC cells | (162) |
| DBH-AS1 | 45 HCC tissues and paired ANTs, male BALB/C nude mice | HepG2, SMMC-7721, Hep3B, MHCC97H, SK-Hep1, LO2, QSG7701 | – | MAPK signaling pathway | HBsAg, tumor size | Promotes proliferation and survival of HCC cells by activating MAPK signaling pathway | (163) |
| DBH-AS1 | 46 HCC tissues and paired ANTs | Huh7, PLC, HepG2, Hep3B, LO2 | miR-138, | AK/Src/ERK signaling pathway | tumor size, TNM stage, lymph node metastasis | Promotes tumorigenesis of HCC through targeting miR-138 by AK/Src/ERK signaling pathway | (164) |
| LINC00152 | BALB/c mic | HCCLM3, HepG2, MHCC97L, SNU449, THLE‐3, LO2 | miR-215, CDK13 | – | – | Its knockdown inhibits proliferation, migration and invasion and induces apoptosis in HCC cells through regulation of miR-215/CDK13 axis | (165) |
| LINC00152 | 70 HCC tissues and paired ANTs, male BALB/c mice | Hep3B, HCCLM3, MCC97H, HepG2 | miR-139, PIK3CA | PI3K/Akt/mTOR signaling pathway | – | Promotes HCC progression through sponging miR-139 and upregulation of PIK3CA | (166) |
| LINC00152 | 80 HCC tissues and paired ANTs, male athymic BALB/c nude mice | Huh7, HCCLM3, Hep3B | miR-193a/b-3p, CCND1 | – | – | Supports cell cycle transition through sponging miR-193a/b-3p and upregulation of CCND1 | (167) |
| AFAP1-AS1 | 156 HCC tissues and paired ANTs, nude mice | LO2, SMMC-7721, Bel-7402, MHCC-97 L, MHCC-97H | – | – | Patient survival, tumor size, TNM stage, vascular invasion | Its silencing attenuates proliferation, migration and invasion and induces apoptosis in HC cells | (168) |
| LNC473 | 70 HCC tissues and paired ANTs | Hep3B, Huh-1, SMMC-7721, PLC/PRF/5, SK-Hep-1 | survivin | – | tumor size, BCLC stage, vascular invasion | Promotes proliferation, invasion and EMT process and suppresses apoptosis in HCC cells via stabilizing survivin | (169) |
| CHRF | 48 HCC tissues and paired ANTs | HepG2, Huh‐7 | miR-21 | PI3K/AKT and Wnt/β-catenin pathways | TNM stage, differentiation, tumors size | Promotes proliferation, cell viability and EMT process in HCC cells through targeting miR-21 | (170) |
| NORAD | 29 HCC tissues and paired ANTs | SMMC‐7721, Huh7, PLC/PRF/5, Hep3B | miR-202-5p | TGF-β pathway | Patient survival, HbsAg, tumor size | Stimulates proliferation, migration and invasion of HCC cells via targeting miR-202-5p | (171) |
| lncPARP1 | 70 HCC tissues and paired ANTs, male BALB/c nude mice | SMMC-7721, HepG2, Huh7, SK-Hep-1, PLC/PRF/5, Bel-7402 | PARP1 | – | Patient survival, elder age, serum level of α-fetoprotein (AFP), tumor size, recurrence | Its knockdown suppresses proliferation, migration, and invasion, while induced apoptosis in HCC cells via regulating PARP1 | (172) |
| lncARSR | 92 HCC tissues and paired ANTs, male athymic BALB/c nude mice | SMMC-7721, HepG2 | PTEN | PI3K/Akt signaling pathway | Patient survival, tumor size, BCLC stage | Promotes doxorubicin resistance of HCC cells through downregulating PTEN and activation of PI3K/Akt signaling pathway | (173) |
| LASP1-AS | 423 HCC tissues and paired ANTs, athymic male BALB/c nude mic | HCCLM, MHCC97H, d PLC/ PRF/5, Hep3B, HepG2, SMMC-7721, Bel‐7402, Huh7 | LASP1 | – | Patient survival, tumor size, tumor encapsulation, TNM stage | Supports proliferation, migration and invasion of HCC cells via upregulation of LASP1 | (174) |
| CCHE1 | 112 HCC tissues and paired ANTs | MHCC97H, HepG2, Hep3B, Huh-7, HCCLM3, L02 | – | ERK/MAPK signaling pathway | Patient survival, tumor number, tumor size, TNM stage | Its knockdown induces growth arrest and apoptosis in HCC cells | (175) |
| TUC338 | 12 HCC tissues and paired ANTs, male nude mice | HepG2, SMMC-7721, BEK-7402, Hep3B, Huh-7 | RASAL1 | – | – | Its down-regulation constrains cell proliferation and invasion and sensitizes HCC cells to sorafenib by activation of RASAL1. | (176) |
| GIHCG | 70 HCC tissues and paired ANTs, male athymic BALB/c nude mice | L02, QSG7701, SMMC7721, Hep3B, Huh7, HCCLM3 | miR-200b/a/429 | – | Patient survival, tumor size, microvascular invasion, BCLC stage | Stimulates proliferation, migration and invasion of HCC cells via epigenetically silencing miR-200b/a/429 | (177) |
| lncAKHE | 60 HCC tissues and paired ANTs, 10 male BALB/c nude mice | LO2, Hep3B, 7402, Huh7, HepG2 | YEATS4 | NOTCH2 signaling pathway | Patient survival | Stimulates proliferation and migration of HCC cells via cooperating with YEATS4 and activation of NOTCH2 signaling | (178) |
| DUXAP10 | 32 HCC tissues and paired ANTs | HepG2, SMMC7721, LO2 | – | PI3K/Akt and Wnt/β-catenin signaling pathway | – | Its knockdown suppresses proliferation, migration and invasion and induces apoptosis in HCC cells | (179) |
| ZEB1-AS1 | 102 HCC tissues and 21 healthy liver samples, athymic BALB/C mice | Huh7, HepG2, Hep3B, SMMC7721, LM3, LO2 | – | – | Patient survival, microvascular invasion, recurrence | Influences tumor growth and metastasis in HCC cells | (180) |
| MYCNOS | 30 HCC tissues and paired ANTs, female BALB/c mice | HL-7702, Huh-7, Hep3B, JHH-7, SNU398 | miR-340, PREX2 | – | Patient survival | Influences proliferation and invasion of HCC cells through sponging miR-340 and upregulation of PREX2 | (181) |
| AGAP2-AS1 | 137 HCC tissues and paired ANTs | LO2, Hep3B, HCCLM3, Huh7, MHCC-97H, SMMC-7721 | miR-16-5p, ANXA11 | AKT signaling pathway | Patient survival, TNM stage, venous invasion, Edmondson, tumor size | Promotes proliferation, migration, invasion and EMT process and suppresses apoptosis in HCC cells through sponging miR-16-5p and upregulation of ANXA11 | (182) |
| Linc00176 | – | HepG2, Huh7, Hep3B, HLE, HLF, HeLa, HEK29 | miR-9, miR-185 | – | Patient survival | Its knockdown disrupts the cell cycle and activates necroptosis in HCC cells through releasing miR-9 and miR-185 | (183) |
| AK002107 | 134 HCC tissues and paired ANTs, BALB/c nu/nu mice | HepG2, MHCC97H, MHCC97L, SMMC7721, Hep3B, BEL7402, LO2 | miR-140-5p, TGFBR1 | – | Patient survival, Child-Pugh stage, AFP, macrovascular invasion, microvascular invasion, tumor size | Induces HCC progression and EMT process through regulating miR-140-5p/TGFBR1 axis | (184) |
| DDX11-AS1 | 40 HCC tissues and paired ANTs, 6 immune-deficient nude mice | (HepG2, SMMC-7721, SK-hep1, Huh7, HCCLM3, LO2 | LATS2 | – | Patient survival, serum AFP, TNM stage | Promotes HCC progression and metastasis by repressing LATS2 expression | (185) |
| GATA3-AS1 | 80 HCC tissues and paired ANTs | Hep3B, HCCLM3 | PTEN, CDKN1A, TP53 | – | Patient survival, tumor size, TNM stage, lymph node metastasis | Promotes proliferation and metastatic ability of HCC cells through repressing PTEN, CDKN1A and TP53 | (186) |
| DLEU1 | 56 HCC tissues and paired ANTs, male BALB/c nude mice | SMMC-7721, Hep3B, HepG2, Huh‐7, LO2 | miR-133a, IGF-1R | PI3K/AKT signaling pathway | Patient survival, TNM stage, vascular metastasis | Endorses HCC progression through sponging miR-133a and regulation of IGF-1R | (187) |
| Lnc-Myd88 | 110 HCC tissues and paired ANTs, BAB/c nude mice | HepG2, SNU423, SMMC-7721, Hep3B, 97H, 97 L, Huh7, L02 | Myd88, H3K27Ac | NF-κB and PI3K/AKT signal pathways | Tumor size, metastasis, Edmondson grade | Endorses proliferation and metastasis of HCC cells through increasing Myd88 expression and by H3K27 modification | (188) |
| KTN1-AS1 | 80 HCC tissues and paired ANTs, mice | Huh7, MHCC97H, SMMC-7721, Bel-7402, LO2 | miR-23c, ERBB2IP | – | Patient survival, tumor size, tumor grade TNM stage | Promotes proliferation and tumor growth of HCC by regulating miR-23c/ERBB2IP axis | (189) |
| Linc-GALH | 108 HCC tissues and paired ANTs, 12 normal liver tissues | Huh7, SNU-423, MHCC-97H, MHCC-97L, SMMC-7721, Hep3B, HepG2, L02 | Gankyrin | – | Patient survival, vascular invasion, intrahepatic metastasis, distant metastasis, | Promotes migration and invasion HCC cells via epigenetically regulating Gankyrin | (190) |
| MITA1 | SCID mice | HepG2, A549, U87, PC3, Huh7, HCCLM3, SK-Hep1, SMMC-7721, LO2, HGC27, U251 | Slug | – | – | Its knockdown suppresses migration and invasion of HCC cells | (191) |
| lnc-UCID | 139 HCC tissues and paired ANTs female NSG mice | HEK293T, LO2, HepG2, QGY-7703 | CDK6 | – | Patient survival | Promotes cell cycle progression and HCC growth through suppressing DHX9-Mediated CDK6 Down-regulation | (192) |
| EIF3J-AS1 | 80 HCC tissues and paired ANTs | HepG2, SMMC-7721, MHCC97H, MHCC97H, LO2 | miR-122-5p, CTNND2 | tumor size, vascular invasion, tumor stage | Its knockdown suppresses proliferation, migration and invasion of HCC cells through regulation of miR-122-5p/CTNND2 axis | (193) | |
| lncRNA n335586 | 3 HBV positive HCC tissues and 3 HBV negative HCC tissues, female athymic BALB/c nude mice | Huh7, HepG2 | miR-924, CKMT1A | – | – | Promotes migration, invasion and EMT process through sponging miR-924 and upregulation of CKMT1A | (194) |
| FGFR3-AS1 | 49 HCC tissues and 15 paired peritumor tissues, male BALB/c nude mice | SMMC-7721, BEL-7404 (7404), Huh7, Hep3B, HepG2, HL-7702 | – | PI3K/AKT signaling pathway | – | Its knockdown suppresses proliferation, migration and invasion and induces apoptosis in HCC cells | (195) |
| LINC00473 | Male nude mice | SMCC-7721, HepG2, Huh-7, HCCLM3, QGY-7703, QSG-7701 | miR-195, HMGA2 | – | – | Contributes to HCC progression through sponging miR-195 and upregulation of HMGA2 | (196) |
| LINC01551 | 60 HCC tissues and paired ANTs | L‐02, MHCC97-H, HepG2, SMCC7721 | miR-122-5p, ADAM10 | – | – | Enhances proliferation, migration and invasion of HCC cells via sponging miR-122-5p and upregulation of ADAM10 | (197) |
| lncRNA-6195 (TCONS_00006195) | 47 HBV-related HCC tissues and ANT | Huh7, HepG2, 293T, L02 | ENO1 | – | Patient survival, Edmondson-Steiner grade | Suppresses proliferation of HCC cells through repressing enzymatic activity of ENO1 and inhibiting the energy metabolism | (198) |
| LINC00511 | 127 HCC tissues and paired ANTs | LO2, Hep3B, HepG2, SMMC-7721, MHCC97H, Huh7, HCCLM3 | miR-424 | – | Patient survival, nodal metastasis, vascular invasion, clinical stage | Promotes proliferation and metastasis of HCC cells through modulating miR-424 | (199) |
| LINC00511 | Expression data of HCC patients obtained from GEO and TCGA | SMCC7721, HepG2, Huh7, Hep3B, L-02 | miR-195, EYA1 | – | Patient survival, tumor stage | Promotes HCC progression through sponging miR-195 and upregulation of EYA1 | (200) |
| linc00462 | 49 HCC tissues and paired ANTs | HCC-LM3, Huh7, SK-hep-1, QSG-7701 | – | PI3K/AKT signaling pathway | portal vein tumor thrombus tumor size, tumor number, BCLC stage | Its down-regulation decreases proliferation, migration and invasion of HCC cells. | (201) |
| NR027113 | 134 HCC tissues and paired ANTs | Bel-7402, SK-HEP-1, PLC/PRF/5, MHCC97H, SMMC-7721 | PI3K/Akt signaling pathway | Patient survival, TNM stage, tumor size | Its down-regulation decreases proliferation, metastasis and EMT process in HCC cells | (202) | |
| ASLNC02525 | 5 HCC tissues and paired ANTs | .HepG2, QGY-7701, SMMC-7721, L-02 | hsa-miR-489-3p, twist1 | – | – | Its silencing suppresses proliferation and invasion of HCC cells through regulating hsa-miR-489-3p/twist1 axis | (203) |
| LncDQ | 84 HCC tissues and paired ANTs, 50 serum samples from HCC patients and 30 serum samples from healthy controls, male BALB/c athymic nude mice | Huh-7, HepG2, HepG3B, SMMC7721, L02 | – | – | Patient survival, tumor stage, lymph node metastasis, tumor number | Its down-regulation decreases proliferation, migration and invasion of HCC cells | (204) |
| LINC00963 | 48 HCC tissues and paired ANTs | L-02, HepG2, HB611, HHCC | – | PI3K/AKT signaling pathway | Patient survival, tumor size, TNM stage | Promotes proliferation of HCC cells through activating PI3K/AKT signaling pathway | (205) |
| DCST1-AS1 | 60 HCC tissues and paired ANTs, immunodeficient mice | L02, HepG2, SMMC-7721, Bel-7404, SK-hep-1 | miR-1254, FAIM2 | – | Patient survival, tumor size | Its knockout suppresses proliferation and induces apoptosis and cell cycle arrest through regulating miR-1254/FAIM2 axis | (206) |
| lncRNA00673 | 55 HCC tissues and paired ANTs, male BALB/c mice | HepG2, Hep3B, MHCC-97H, L02 | – | Notch signaling pathway | – | Its knockdown suppresses proliferation and induces cell cycle arrest and apoptosis in HCC cells | (207) |
| TGFB2-AS1 | – | HepG2 | – | – | Tumor stage | Its down-regulation decreases proliferation, migration and invasion and induces apoptosis in HCC cells | (208) |
| FLVCR1-AS1 | 60 HCC tissues and paired ANTs, BALB/c nude mice | LO2, Hep3B, HepG2, Huh7, PLC/PRF-5 | miR-513c, MET | – | TNM stage, tumor size | Promotes HCC development and progression through sponging miR-513c and upregulation of MET | (209) |
| LINC00707 | 12 BALB/c mice | SMCC7721, HepG2, Hep3B, SNU-449, Huh7, LO2 | miR-206, CDK14 | – | – | Promotes HCC progression via sponging miR-206 and upregulation of CDK14 | (210) |
| lncZic2 | 12 advanced HCC tissues, 7 early HCC tissues and 19 peritumor specimens, BALB/c nude mice | – | MARCKS, MARCKSL1 | – | – | Regulates self-renewal of liver tumor-initiating cells by increasing MARCKS and MARCKSL1 expression through interacting with BRG1 | (211) |
| GHET1 | 68 HCC tissues and paired ANTs | HepG2, Hep3B, Bel-7402, SMMC-7721 HCC, L02 | KLF2 | – | Patient survival, vascular invasion, cirrhosis, tumor size, edmindson grade | Promotes proliferation of HCC cells through epigenetically silencing KLF2 | () |
| lncRNA 00152 | 58 HCC tissues and paired ANTs | MHCC97, Huh7, HB611, LO2 | – | JAK2/STAT3 signaling pathway | tumor stage, tumor size | Promotes cell proliferation and cell cycle progression by activating JAK2/STAT3 signaling pathway | (212) |
| OR3A4 | 78 HCC tissues and paired ANTs | L02, HUVECs, (Huh7, SMMC-7721, HepG2, Hep3B | – | AGGF1/akt/mTOR pathway | Patient survival, tumor size, tumor differentiation, Edmondson Grade, vascular invasion | Its down-regulation decreases proliferation, migration, invasion and angiogenesis in HCC cells. | (213) |
| PAPAS | 74 HCC tissues and paired ANTs, plasma samples from 74 HCC patients and 52 healthy controls | SNU-398, SNU‐182 | miR-188-5p | – | – | Promotes HCC cells proliferation through interacting with miR-188-5p | (214) |
| LINC01433 | 12 BALB/c mice | Huh‐7, HepG2, Hep3B, MHCC97L, SMCC-7721, LO2 | miR-1301, STAT3 | – | – | Promotes proliferation, invasion and colony formation ability through modulating miR-1301/STAT3 axis | (215) |
| PITPNA-AS1 | 60 HCC tissues and paired ANTs, BALB/c nude mice | HepG2, SMMC-7721, HCCLM3, Hep3B, L02, 293T | miR-876-5p, WNT5A | – | Patient survival, metastasis, TNM stage | Promotes proliferation, migration and EMT process in HCC cells through targeting miR-876-5p and modulating WNT5A expression | (216) |
| BC200 | 45 HCC tissues and paired ANTs, 18 male BALB/c nude mice | HepG2 | c−Myc | – | – | Promotes HCC cells migration but has no significant effect on cell proliferation | (217) |
| LINC00470 | 80 HCC tissues and paired ANTs | LO2, Hep3B, SK-Hep-1, SMMC-7721, Huh7, PLC/PRF/5, HepG2 | NF45/NF90, cyclin E1 | – | Patient survival, tumor size, TNM stage | Promotes proliferation of HCC cells via interacting with NF45/NF90 and stabilizing cyclin E1 | (218) |
| CASC15 | 42 HCC tissues and paired ANTs, female BALB/c nude mice | HUH7, HCCLM3 | miR-33a-5p, TWIST1 | – | – | Promotes proliferation, migration and invasion and reduces apoptosis in HCC cells via sponging miR-33a-5p and upregulation of TWIST1 | (219) |
| LINC00460 | 60 HCC tissues and paired ANTs, serum samples from 60 patients and 60 healthy controls, 12 BALB/c nude mice | HepG2, Hep3B, SNU-449, THLE-3 cells, HCCLM3, Huh-7, LO2 | miR-485-5p, PAK1 | – | tumor differentiation grade, tumor dimension, capsular integrity, TNM stage, metastasis | Promotes HCC progression by sponging miR-485-5p and upregulation of PAK1 | (220) |
| TINCR | 60 HCC tissues and paired ANTs | H1581, SNU-475, | miR-214-5p, ROCK1 | – | tumor size, TNM stage | Promotes migration and invasion of HCC cells via sponging miR-214-5p and upregulation of ROCK1 | (221) |
| RHPN1-AS1 | 40 HCC tissues and paired ANTs | Hep3B, Huh7, SMMC-7721, MHCC97, Bel-7402, QSG-7701, HEK-293T | miR-596, IGF2BP2 | – | Patient survival, lymphatic metastasis, AFP | Promotes proliferation and metastasis and reduces apoptosis by regulating miR-596/IGF2BP2 axis | (222) |
Function of over-activated lncRNAs in HCC (ANT, adjacent non-cancerous tissue; HBS Ag, hepatitis B surface antigen).
Down-Regulated lncRNAs in HCC
Through a high throughput approach, Ni et al. have identified uc.134 as a novel lncRNA which is under-expressed in a highly aggressive HCC cell line. They further verified its down-regulation in clinical HCC samples compared with paired nearby tissues. Notably, down-regulation of uc.134 has been related with poor prognosis of HCC patients. Functionally, this lncRNA suppresses cell proliferation, invasion, and metastasis through binding with CUL4A suppressing its nuclear export. Besides, uc.134 suppresses the CUL4A-associted ubiquitination of LATS1 and enhances YAPS127 phosphorylation which results in down-regulation of YAP target genes of YAP (223). LncRNA-PRAL has been shown to suppress HCC growth and stimulate apoptosis via a p53-dependent route. Certain motifs at the 5’ end of this lncRNA have been identified that participate in competitive inhibition of MDM2-dependent p53 ubiquitination (224). Expression of the lncRNA-LET has been decreased in HCC. Further experiments have shown the role of hypoxia-induced histone deacetylase 3 in down-regulation of this lncRNA. Notably, repression of lncRNA-LET has been identified as an important step in the stabilization of nuclear factor 90 protein and subsequent hypoxia-associated tumor cell invasion. The association between down-regulation of lncRNA-LET and metastatic potential of HCC has also been verified in clinical samples (225). TSLNC8 is also down-regulated in HCC samples. Down-regulation of this lncRNA in HCC has been shown to confer malignant phenotype. TSLNC8 competitively interacts with transketolase and STAT3 and alters the phosphorylation patterns and transcriptional activity of STAT3 leading to suppression of the IL-6-STAT3 signaling (226). CASC2 is another down-regulated lncRNAs in HCC samples, particularly in the samples obtained patients with aggressive and recurrent forms of HCC. CASC2 suppresses migration and invasive properties of HCC cells and inhibits EMT program in these cells. Mechanistically, it serves as a competing endogenous RNA for miR-367 to increase expression of its target gene FBXW7. Notably, CASC2 down-regulation and miR-367 up-regulation have been associated with the metastasis-associated characteristics in the clinical samples (227). Table 2 displays the impact of down-regulated lncRNAs in HCC.
Table 2
| lncRNA | Sample | Assessed cell line | Gene interaction | Signaling pathway | Association with clinical features | Function | Reference |
|---|---|---|---|---|---|---|---|
| PSTAR | 127 HCC tissues and ANTs | PHH, HUCPM, HepG2, MHCC-97H, HCCLM3, Hep3B, Huh7, HEK293T, HCT116 | p53, hnRNP K | p53 signaling pathway | Patient survival, tumor size, tumor stage | Suppresses proliferation and tumorigenicity of HCC cells by promoting p53 signaling and cell cycle arrest | (228) |
| TPTEP1 | 32 primary HCC tissues and paired ANTs, 18 male BALB/c nude mice | HepG2, SMMC-7721, QGY-7703, Huh-7, MHCC97h, SNU-449, Sk-hep1, and L02 | STAT3 | – | – | Represses proliferation, invasion and tumorigenicity of HCC cells through inhibiting STAT3 phosphorylation | (229) |
| CASC2 | 75 HCC tissues and ANTs, nude mice | MHCC-97L, Hep-3B, HepG2, Huh7, SMMC-7721, MHCC-97H, LO2 | miR-367, FBXW7 | – | Patient survival, venous infiltration, high Edmondson-Steiner grading, TNM tumor stage | Inhibit migration, invasion and EMT process by sponging miR-367 and upregulation of FBXW7 | (227) |
| CASC2 | 30 HCC tissues and paired ANTs | LO2, HepG2, Hep3B, QSG-7701, SMMC-7721, Huh-7 | miR-183 | Wnt/β-catenin signaling pathway | – | Represses cell viability, colony formation, migration, and invasion through targeting miR-183 | (230) |
| CASC2 | 50 HCC tissues and paired ANTs | HepG2, HuH7, Hep3B, SMMC7221, Bel7402, LO2 | – | MAPK signaling pathway | – | Its overexpression suppresses proliferation, migration and invasion and induces apoptosis in HCC cells | (231) |
| CASC2 | 80 HCC tissues and paired ANTs | HepG2, SMMC-7721, Hep3B, Huh-7, L02 | miR-362-5p | NF-κB signaling pathway | tumor size, differentiation statues | Its overexpression suppresses migration and invasiveness of HCC cells through affecting miR-362-5p. | (232) |
| CASC2 | 20 HCC tissues and paired ANTs, BALB/c nude mice | HepG2, HuH7 | miR-24-3p | – | – | Suppresses cell viability and induces apoptosis in HCC cells via regulating miR-24-3p | (233) |
| EPB41L4A-AS2 | 10 HCC tissues and 10 normal tissues, Neonatal B6C3F1 mice | SMMC-7721, QGY-7703, QSG-7701 | miR-301a-5p, FOXL1 | – | – | Its upregulation inhibits proliferation, migration and invasion by sponging miR-301a-5p and upregulation of FOXL1 | (234) |
| LINC00467 | 65 HCC tissues and paired ANTs | SMMC-7721, HepG2 | miR-9-5a, PPARA | – | metastasis | Its ectopic expression reduces proliferation, migration and invasive features of HCC cells through sponging miR-9-5a and increasing PPARA. | (235) |
| lnc-DILC | 195 HCC tissues and paired ANTs, NOD-SCID mice | Huh7, HepG2, CSQT-2 | IL-6 | JAK2/STAT3 activation | Patient survival | Suppresses liver cancer stem cell expansion through inhibition of autocrine IL-6/STAT3 signaling. | (236) |
| lnc-FTX | 129 HCC tissues and paired ANTs, | SMMC-7721, HCCLM3, Hep3B, HepG2, Huh7, 97H, GSG7701 | miR-374a, MCM2 | Wnt/β-catenin signaling pathway | Patient survival | Suppresses proliferation, invasion and EMT process in HCC cells through physically binding miR-374a and MCM2 | (237) |
| LINC00472 | 109 HCC tissues and 35 ANTs | LO2, HepG2, BEL7404, Hep3B, SMMC-7721, Huh-7 | miR-93-5p, PDCD4 | – | Patient survival | Its forced expression suppressed cell proliferation, migration and invasion and promotes apoptosis through miR-93-5p/PDCD4 axis | (238) |
| FENDRR | 30 HCC tissues and paired ANTs, BALB/c male nude mice | HepG2, Hep3B, LO2 | GPC3 | – | – | Suppresses proliferation, migration and invasion and induces apoptosis in HCC cells through epigenetically silencing GPC3 | (239) |
| TSLNC8 | 120 HCC tissues and paired ANTs, nude mice | Huh-7, SNU-449, SMMC-7721 | STAT3 | – | Patient survival | Suppresses cell proliferation and metastasis of HCC cells | (226) |
| miR503HG | 93 HCC tissues and paired ANTs | SMMC-7721, Huh7, L02 | HNRNPA2B1 | NF-κB signaling pathway | Patient survival, tumor recurrence | Represses HCC cells invasion and metastasis through stimulation of HNRNPA2B1 degradation | (151) |
| MEG3 | 54 HCC tissues and paired ANTs, serum samples from 54 HCC patients and 54 healthy controls | Hep G2, SNU-398, C3A, AML12, | TGF-β1 | – | Patient survival, distant tumor metastasis | Its silencing promotes proliferation, migration and invasion in HCC cells through upregulation of TGF-β1 | (240) |
| MEG3 | 30 HCC tissues and paired ANTs | 293T, SK-HEP-1, Huh7 | miR-9-5p, SOX11 | – | TNM stage, metastasis | Its overexpression represses cell growth and promotes apoptosis in HCC cells by sponging miR-9-5p and upregulation of SOX11 | (241) |
| TSLD8 | 108 HCC tissues and paired ANTs | SMMC-7721, Huh7, HepG2, Hep3B, L02, HEK293T | WWOX | – | TNM stages, tumor dimension, metastatic ability, occurrence of cancer embolus | Inhibits migration and cell viability of HCC cells through stabilizing WWOX | (241) |
| Lnc00312 | 23 HCC tissues and paired ANTs, female SCID mice | HepG2, MKN-74 | cyclin B1 | – | – | Inhibits cell proliferation and induces apoptosis and cell cycle arrest through downregulation of cyclin B1 | (242) |
| lncNRON | 215 HCC tissues and paired ANTs, 5 male nude mice | QGY-7703, HepG2, BEL-7404, Hep3B, SMMC-7721, MHCC97, L02 | NFAT | – | Patient survival, tumor size, tumor differentiation, Vascular tumor thrombus | Suppresses proliferation, migration and invasion of HC cells | (243) |
| PTENP1 | – | Mahlavu | miR-17, miR-19b, miR-20a, PTEN, PHLPP | PI3K/AKT signaling pathway | – | Its overexpression suppresses proliferation, migration and invasion and supports autophagy and apoptosis in HCC cells | (244) |
| LIN00607 | 159 HCC tissues and paired ANTs, nude mice | MHCC97H, HCCLM3, PLC, Hep3B, HepG2, 7721 | p65, p53 | – | Patient survival | Its overexpression reduces cell proliferation and induces apoptosis in HCC cells through suppression of p65 transcription | (245) |
| AOC4P | 108 HCC tissues and paired ANTs, male BALB/C nude mice | J7, SK-Hep1 | Vimentin | – | Patient survival, clinical stage, capsule invasion, vessel invasion | Constrains proliferation and metastasis of HCC cells by increasing Vimentin degradation and inhibition of EMT process | (246) |
| AK058003 | 50 HCC tissues and paired ANTs, male athymic BALB/c nude mice | HepG2, SK-Hep1, HEK 293T | HuR, γ-synuclein | – | – | Suppresses proliferation and metastasis of HCC cells by interacting with HuR and inhibiting γ-synuclein expression | (247) |
| Linc-USP16 | 70 HCC tissues and paired ANTs, | MHCC97H, MHCC97L, HepG2, SMMC-7721, LO2, BEL7402 | miR-21, miR-590-5p, PTEN | AKT signaling pathway | tumor size, clinical stage, metastasis | Suppresses proliferation and migration of HCC cells through regulation of miR-21/miR-590-5p/PTEN route | (247) |
| FER1L4 | 35 HCC tissues and paired ANTs, 14 Female athymic BALB/c mice | LO2, Hep3B Huh7, 293T | PTEN | – | – | Suppresses proliferation of HCC cells via regulating PTEN | (248) |
| FER1L4 | 36 HCC tissues and paired ANTs, Female nude (BALB/c-nu) mice | HepG2, Huh7, Hep3B, HCCM3, LO2 | miR-106a-5p | – | – | Constrains proliferation, invasion and tumorigenicity of HCC cells via targeting miR-106a-5p | (249) |
| FER1L4 | 31 HCC tissues and paired ANTs | HepG‐2, Hep3b, SMMC‐7721, L‐02 | – | PII3K/AKT signaling pathway | – | Its overexpression reduces cell proliferation, migration and invasion and induces apoptosis | (250) |
| PANDA | 48 HCC tissues and paired ANTs, immunodeficient mice | HCC LM3, Huh7 | – | – | – | Its overexpression enhances proliferation of HCC cells by repressing senescence associated inflammatory factor IL8 | (251) |
| HHIP-AS1 | 60 HCC tissues and paired ANTs | Hep3B, PLC/PRF/5, Huh7, HepG2, MHCC-97 h | HHIP | – | tumor size, metastasis, TNM stage | Constrains proliferation, migration and invasion and induces apoptosis in HCC cells via stabilizing HHIP | (252) |
| XIST | 40 HCC tissues and paired ANTs | HepG2 | miR-155-5p | – | – | Its overexpression inhibits HCC cell growth by targeting miR-155-5p | (253) |
| JPX | 40 HCC tissues and paired ANTs | HepG2 | XIST | – | – | Its overexpression HCC cell growth through upregulation of v | (253) |
| uc.134 | 170 paraffin-embedded samples of HCC tissues and ANTs, male BALB/c nude mice | MHCC97, HCCLM3, MHCC97L, Huh7, L02, HepG2, Bel7402 | LATS1, CUL4A | – | Patient survival, TNM stage, lymph node metastasis, tumor number, Serum AFP, | Constrains proliferation, invasion and metastasis of HCC cells through suppressing CUL4A-mediated ubiquitination of LATS1 | (223) |
| C1QTNF1-AS1 | 11 HCC tissues and paired ANTs, 12 male BALB/C nude mice | HepG2, Huh7 | miR-221-3p, SOCS3 | JAK/STAT signaling pathway | – | Its overexpression inhibits proliferation, migration and invasion of HCC cells through targeting miR-221-3p and upregulation of SOCS3 | (254) |
| GAS8-AS1 | 82 HCC tissues and paired ANTs, male nude BALB/c mice | HepG2, SMMC7721 | GAS8 | – | Patient survival | Suppresses proliferation, migration and invasion and induces apoptosis by epigenetically activating GAS8 | (255) |
| LINC00657 | 49 HCC tissues and paired ANTs, female nude (BALB/c-nu) mice | HepG2, Huh7, Hep3B, Bel-7402, SMMC-7721, HCCM3 | miR-106a-5p, PTEN | – | Patient survival, tumor size, vascular invasion, TNM stage | Suppresses proliferation, migration and invasion through sponging miR-106a-5p and regulation of PTEN expression | (256) |
| Linc-cdh4-2 (TCONS_00027978) | – | SK-Hep-1, Huh7 | R-cadherin | – | – | Represses migration and invasion of HCC cells through regulation of R-cadherin | (257) |
| MAGI2-AS3 | 88 HCC tissues and paired ANTs, 12 male BABL/c nude mice | L02, HepG2, Hep3B, MHCC‐97H | miR-374b-5p, SMG1 | – | Patient survival, tumor size, lymph node metastasis, TNM stage | Suppresses proliferation and migration of HCC cells via sponging miR-374b-5p and increasing SMG1 | (258) |
| LINC01093 | 70 HCC tissues and paired ANTs, BALB/c-nu/nu mice | Huh7, BEL-7402 | IGF2BP1, GLI1 | – | Patient survival, cancer embolus, TNM stage | Suppresses proliferation and metastasis of HCC cells via interaction with IGF2BP1 and facilitation of GLI1 degradation | (259) |
| GAS5 | 50 HCC tissues and paired ANTs | Huh7, Hep3B, HepG2, QGY-7701, MHCC97L, HCCLM9he, L02 | vimentin | – | Patient survival, PVTT, histologic grade | Inhibits proliferation and invasion of HCC cells through regulating Vimentin | (260) |
| GAS5 | 32 HCC tissues and paired ANTs | Bel-7402, SMMC-7721, HCCLM3, L-02 | miR-21 | – | Patient survival, TNM stage, tumor size | Its overexpression suppresses migration and invasion of HCC cells through targeting miR-21 | (261) |
| GAS5 | 32 HCC tissues and paired ANTs, mice | HepG2, HepB3, LO2 | miR-21, PTEN | – | Patient survival | Its downregulation promotes proliferation and drug resistance HCC cells through reducing PTEN | (262) |
| GAS5 | 38 HCC tissues and paired ANTs | Lo-2, HepG2, Huh7 | miR-222 | VEGF signaling pathway | Patient survival | Enhances sensitivity of HCC cells to cisplatin through sponging miR-222 | (262) |
| SchLAH | 132 HCC tissues and paired ANTs, BALB/c nude mice | HepG2, Hep3B, SMMC7721 | FUS | – | Patient survival | Represses migration and lung metastasis of HCC cells via interacting with FUS | (263) |
| NKILA | 54 HCC tissues and paired ANTs | QSG-7701, SMMC-7721, Hep3B, HCCLM3, HepG2 | – | NF-κB signaling | Patient survival | Its overexpression enhances baicalein effect on inhibition of proliferation and migration and induction of apoptosis | (264) |
| LINC00261 | 66 HCC tissues and paired ANTs | SMCC-7721, MHCC97L, MHCC97H, LO2 | – | Notch signaling pathway | Patient survival, tumor size, TNM stage | Inhibits proliferation, colony formation, invasion and EMT process | (265) |
| MIR31HG | 42 HCC tissues and paired ANTs, BALB/c nude mice | SMMC7721, HepG2, Huh7, SK-hep1, L02 | miR-575, ST7L | – | Patient survival, TNM stage, tumor size, tumor nodule number, vascular invasion | Suppresses proliferation, migration and invasion of HCC cells through sponging miR-575 and regulation of ST7L expression | (266) |
| LINC01554 | 167 HCC tissues and paired ANTs | BEL7402, QGY7701, QGY7703, SMMC7721, PLC8024, HepG2, Huh7, Hep3B | miR-365a, PKM2 | Akt/mTOR signaling pathway | Patient survival, tumor invasion, tumor size, tumor stage | Inhibits cell growth, colony formation in soft agar, foci formation, and tumor formation through downregulation of PKM2 | (267) |
| FAM99B | 80 HCC tissues and paired ANTs | MHCC97L, MHCC97H, HCCLM3, Huh-7, HepG2, Hep3B | – | – | Patient survival, vascular invasion, histologic grade, T stage | Its overexpression suppresses proliferation, migration and invasion of HCC cells | (268) |
| RGMB-AS1 | 108 HCC tissues and 25 ANTs | QGY-7703, HuH7, BEL7402, HepG2 | RGMB | – | Patient survival, clinical stage, tumor size, metastasis | Its overexpression represses proliferation, migration and invasion of HCC cells | (269) |
| LINC00052 | 12 HCC tissues and paired ANTs | SMMC7721, HepG2, SK-hep1, Huh7, L02, 293T | miR-101-3p, SOX9 | – | – | Constrains proliferation and metastasis via affecting miR-101-3p and suppressing SOX9 | (270) |
| DGCR5 | – | HepG2, Hep3B, MHCC-97L, SNU-449, MHCC-97H, SMCC7721, THLE-3 | miR-346, KLF14 | – | – | Its overexpression attenuates proliferation, migration and invasion of HCC cells through sponging miR-346 and modulating KLF14 expression | (271) |
| ID2-AS1 | 144 HCC tissues and paired ANTs, NOD-SCID mice | MHCC97L, MHCC97H, HCCLM3, Huh7, HepG2-C3A, SK-Hep1, HEK-293T | ID2 | – | Patient survival | Represses migration, invasion and metastasis of HCC cells via binding to HDAC8 and regulation of ID2 expression | (272) |
| F11-AS1 | – | HepG2, Hep3B, Huh-6, SMMC7721, LO2 | miR-3146, PTEN | – | – | Represses HCC progression via acting as ceRNA for miR-3146 and affecting PTEN level | (273) |
List of under-expressed lncRNAs in HCC (ANT, adjacent non-cancerous tissue).
Diagnostic and Prognostic Impact of lncRNAs in HCC
Expression patterns of several lncRNAs have been related with overall survival or disease-free survival of patients with liver neoplasm. Oncogenic lncRNAs which decrease survival of HCC patients include NEAT1, PTTG3P, UBE2CP3, LINC00461, MALAT1, MNX1-AS1, MCM3AP-AS1, ANRIL, AWPPH, PVT1, SNHG1, ENST00000429227.1, LINC00665, CRNDE, FOXD2-AS1, HULC and some other lncRNAs. Instead, low expressions of several tumor suppressor lncRNAs namely PSTAR, CASC2, lnc-FTX, LINC00472, TSLNC8, miR503HG, MEG3, LIN00607, AOC4P, uc.134, GAS8-AS1, LINC00657, MAGI2-AS3, LINC01093, GAS5, SchLAH, and NKILA predict patients’ outcome. Univariate/multivariate cox regression analyses have confirmed the role of these lncRNAs in the determination of HCC prognosis. Table 3 lists the results of studies which evaluated the prognostic roles of lncRNAs in patients with HCC.
Table 3
| lncRNA | Sample number | Kaplan-Meier analysis | Univariate cox regression | Multivariate cox regression | Reference |
|---|---|---|---|---|---|
| NEAT1 | 40 HCC specimens and paired ANTs | Its elevated level is related with short OS. | – | – | () |
| NEAT1 | 86 HCC specimens and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic factor for OS | () |
| PTTG3P | 90 paraffin-embedded HCC specimens and ANTs | Its elevated level is related with low OS. | – | an independent prognostic factor for OS | () |
| UBE2CP3 | 46 HCC specimens and ANTs | Its elevated level is related with poor OS. | – | – | () |
| LINC00461 | 87 HCC specimens and paired ANTs | Its elevated level is related with decreased OS. | – | – | () |
| MALAT1 | 56 HCC specimens and paired ANTs | Its elevated level is related with decreased OS. | – | – | () |
| MNX1-AS1 | 81 HCC specimens and paired ANTs | Its elevated level is related with poor OS. | – | – | (37) |
| MCM3AP-AS1 | 80 HCC specimens and paired ANTs | Its elevated level is related with shorter OS. | – | – | () |
| ANRIL | 130 tissues and paired ANTs | Its elevated level is related with low OS. | correlated with OS | an independent prognostic marker for OS | (49) |
| AWPPH | 88 HCC specimens and paired ANT | Its elevated level is related with poor DFS and OS. | – | an independent prognostic factor for RFS and OS | (51) |
| PVT1 | 48 HCC specimens and paired ANTs | Its elevated level is related with poor OS. | – | – | (53) |
| SNHG1 | 82 HCC specimens and paired ANTs | Its elevated level is related with poor RFS and OS. | – | – | (56) |
| ENST00000429227.1 | 161 HCC specimens and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic marker for OS | (58) |
| LINC00665 | 76 HCC specimens and paired ANTs | Its elevated level is related with shorter OS | – | – | (63) |
| CRNDE | 23 HCC specimens and paired ANTs | Its elevated level is related with shorter DFS and OS. | – | – | (65) |
| FOXD2-AS1 | 88 HCC specimens and paired ANTs | Its elevated level is related with poor OS. | – | – | (70) |
| HULC | 41 HCC specimens and paired ANTs | Its elevated level is related with shorter OS. | correlated with OS | Its expression pattern is not an independent prognostic marker for PFS and OS. | (76) |
| SBF2-AS1 | 134 HCC specimens and paired ANTs | Its elevated level is related with shorter OS. | correlated with OS | Its expression pattern is not an independent prognostic marker for OS. | (78) |
| UC001kfo | 82 HCC tissues and 20 ANTs | Its elevated level is related with poor progression-free survival (PFS) and OS. | correlated with PFS and OS. | an independent prognostic marker for PFS and OS | (79) |
| LUCAT1 | 90 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic marker for OS | (82) |
| AK001796 | 73 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | an independent prognostic marker for OS | (83) |
| FEZF1-AS1 | 139 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (84) |
| MINCR | 161 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic marker for OS | (85) |
| XIST | 88 HCC tissues and paired ANTs | Its elevated level is related with short DFS. | – | – | (88) |
| XIST | 52 HCC tissues and paired ANTs | Its elevated level is related with poor survival of HCC patients. | – | – | (89) |
| TRPM2-AS | 108 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (90) |
| LSINCT5 | 126 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (92) |
| XLOC | 68 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | an independent prognostic marker for OS | (93) |
| URHC | 52 HCC tissues and paired ANTs | Its elevated level is related with short OS after surgery. | – | – | (96) |
| RUSC1-AS-N | 66 HCC tissues and paired ANTs | Its elevated level is related with short RFS and OS. | – | – | (99) |
| CCAT1 | 66 HCC tissues and paired ANTs | Its elevated level is related with low RFS and OS. | – | – | (101) |
| SNHG16 | 71 HCC tissues and paired ANTs | Its elevated level is related with poor DFS and OS. | correlated with OS | an independent prognostic marker for OS | (105) |
| SNHG12 | 48 HCC tissues and paired ANTs | Its elevated level is related with poor RFS and OS. | – | – | (108) |
| SNHG20 | 96 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (109) |
| SNHG5 | 48 HCC tissues and paired ANTs | Its elevated level is related with poor RFS and OS. | correlated with RFS and OS | an independent prognostic marker for RFS and OS | (110) |
| SNHG6-003 | 52 HCC tissues and paired ANTs, FFPE tissues from 160 patients | Its elevated level is related with poor DFS and OS. | correlated with OS | an independent prognostic marker for OS | (113) |
| SNHG7 | 40 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | – | (114) |
| SNHG7 | 80 HCC tissues and paired ANTs | Its elevated level is related with short OS. | – | – | (115) |
| Sox2ot | 84 HCC tissues and ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic marker for OS | (119) |
| SPRY4-IT1 | 82 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (121) |
| PANDAR | 482 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic marker for OS | (122) |
| CARLo-5 | 97 HCC tissues and paired ANTs | Its elevated level is related with shorter DFS and OS. | correlated with DFS and OS | an independent risk factor for DFS and OS | (124) |
| PlncRNA-1 | 84 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (126) |
| PCAT-14 | 39 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (129) |
| DLX6-AS1 | 60 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | (131) | |
| TP73-AS1 | 84 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (138) |
| HANR | 35 HCC tissues and paired ANTs, | Its elevated level is related with poor OS. | – | – | (140) |
| lncRNA FAL1 | 30 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (143) |
| CDKN2B-AS1 | 100 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (144) |
| lncRNA-PDPK2P | 60 HCC tissues and paired ANTs, | Its elevated level is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (147) |
| SOX9-AS1 | 67 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | – | (150) |
| SOX21-AS1 | 68 HCC tissues and paired ANTs | Its elevated level is related with shorter OS. | – | an independent prognostic factor for OS | (151) |
| HOXA11-AS | 66 HCC tissues and paired ANTs | Its elevated level is related with shorter OS. | – | – | (152) |
| lncRNA-ATB | 72 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | – | (156) |
| OSER1-AS1 | 34 HCC tissues and paired ANTs | Its elevated level is related with shorter DFS and OS. | – | – | (161) |
| AFAP1-AS1 | 156 HCC tissues and paired ANTs | Its elevated level is related with shorter DFS and OS. | – | – | (168) |
| LNC473 | 70 HCC tissues and paired ANTs | Its elevated level is related with low OS | – | – | (169) |
| NORAD | 29 HCC tissues and paired ANTs | Its elevated level is related with shorter DFS and OS | correlated with OS | an independent prognostic factor for OS | (171) |
| lncPARP1 | 70 HCC tissues and paired ANTs | Its elevated level is related with shorter DFS and OS. | – | – | (172) |
| lncARSR | 92 HCC tissues and paired ANTs | Its elevated level is related with shorter RFS and OS. | – | – | (173) |
| LASP1-AS | 423 HCC tissues and paired ANTs | Its elevated level is related with poor RFS and OS. | correlated with RFS and OS | an independent prognostic factor for RFS and OS | (174) |
| CCHE1 | 112 HCC tissues and paired ANTs | Its elevated level is related with low OS. | correlated with OS | an independent prognostic factor for OS | (175) |
| GIHCG | 70 HCC tissues and paired ANTs | Its elevated level is related with low RFS and OS. | – | – | (177) |
| lncAKHE | 60 HCC tissues and paired ANTs | Its elevated level is related with low DFS and OS. | – | – | (178) |
| ZEB1-AS1 | 102 HCC tissues and 21 healthy liver samples | Its elevated level is related with low RFS and OS. | – | an independent prognostic factor for survival | (180) |
| MYCNOS | 30 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (181) |
| AGAP2-AS1 | 137 HCC tissues and paired ANTs | Its elevated level is related with poor DFS and OS. | – | – | (182) |
| AK002107 | 134 HCC tissues and paired ANTs | Its elevated level is related with poor DFS and OS. | – | an independent prognostic factor for DFS and OS | (184) |
| DDX11-AS1 | 40 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (185) |
| GATA3-AS1 | 80 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | – | (186) |
| DLEU1 | 56 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | – | (187) |
| KTN1-AS1 | 80 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | – | (189) |
| Linc-GALH | 108 HCC tissues and paired ANTs, 12 normal liver tissues | Its elevated level is related with poor RFS and OS. | – | – | (190) |
| LINC00511 | 127 HCC tissues and paired ANTs | Its elevated level is related with low OS | correlated with OS | an independent prognostic factor for OS | (199) |
| NR027113 | 134 HCC tissues and paired ANTs | Its elevated level is related with poor DFS and OS. | – | an independent prognostic factor for survival | (202) |
| LncDQ | 84 HCC tissues and paired ANTs, 50 serum samples from HCC patients and 30 serum samples from healthy controls | Its elevated level is related with low OS. | correlated with OS | an independent prognostic factor for OS | (204) |
| GHET1 | 68 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | an independent prognostic factor for OS | () |
| OR3A4 | 78 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | an independent prognostic factor for HCC | (213) |
| PITPNA-AS1 | 60 HCC tissues and paired ANTs | Its elevated level is related with poor OS. | – | – | (216) |
| AK021443 | 193 HCC tissues and paired ANTs | Its elevated level is related with low OS. | correlated with OS | an independent prognostic factor for OS | (274) |
| UCA1 | Serum samples from 105 HCC patients, 105 persons with benign liver diseases and 105 healthy controls | Its elevated level is related with low OS. | correlated with prognosis | an independent prognostic factor for HCC | (275) |
| SNHG15 | 105 HCC tissues and paired ANTs | Its elevated level is related with low OS. | correlated with OS | an independent prognostic factor for OS | (276) |
| PSTAR | 127 HCC tissues and ANTs | Its low expression is related with poor OS and RFS. | – | an independent prognostic factor for OS and RFS | (228) |
| CASC2 | 75 HCC tissues and ANTs | Its low expression is related with poor OS and DFS. | – | – | (227) |
| lnc-FTX | 129 HCC tissues and paired ANTs | Its low expression is related with poor OS and RFS. | – | – | (237) |
| LINC00472 | 109 HCC tissues and 35 ANTs | Its expression is correlated with short OS. | – | – | (238) |
| TSLNC8 | 120 HCC tissues and paired ANTs | Its low expression is related with low OS. | – | – | (226) |
| miR503HG | 93 HCC tissues and paired ANTs | Its expression level is related with TTR and OS. | correlated with TTR and OS | an independent prognostic factor for TTR and OS | (151) |
| MEG3 | serum samples from 54 HCC patients and 54 healthy controls | Its low expression is related with shorter survival time. | – | – | (240) |
| LIN00607 | 159 HCC tissues and paired ANTs | Its low expression is related with low OS. | – | – | (245) |
| AOC4P | 108 HCC tissues and paired ANTs | Its low expression is related with low DFS and OS. | – | an independent prognostic factor for DFS and OS | (246) |
| uc.134 | 170 paraffin-embedded samples of HCC tissues and ANTs | Its low expression is related with low OS. | – | – | (223) |
| GAS8-AS1 | 82 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | – | (255) |
| LINC00657 | 49 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | – | (256) |
| MAGI2-AS3 | 88 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | an independent prognostic factor for OS | (258) |
| LINC01093 | 70 HCC tissues and paired ANTs | Its low expression is related with short OS. | correlated with OS | an independent prognostic marker for OS | (259) |
| GAS5 | 50 HCC tissues and paired ANTs | Its low expression is related with short OS. | correlated with OS | an independent prognostic marker for OS | (260) |
| GAS5 | 71 HCC tissues and paired ANTs | Its low expression is related with short OS. | correlated with OS | an independent prognostic marker for OS | (277) |
| GAS5 | 38 HCC tissues and paired ANTs | Its low expression is related with short OS. | – | – | (262) |
| SchLAH | 132 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | – | (263) |
| NKILA | 54 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | – | (264) |
| LINC00261 | 66 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | – | (265) |
| MIR31HG | 42 HCC tissues and paired ANTs | Its low expression is related with poor OS. | – | – | (266) |
| LINC01554 | 167 HCC tissues and paired ANTs | Its low expression is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (267) |
| RGMB-AS1 | 108 HCC tissues and 25 ANTs | Its low expression is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (269) |
| ID2-AS1 | 144 HCC tissues and paired ANTs | Its low expression is related with poor OS. | correlated with OS | an independent prognostic factor for OS | (272) |
| CCAT2 | 122 HCC tissues and paired ANTs | Its elevated level is related with low OS. | – | an independent prognostic factor for OS | (278) |
| GAS5-AS1 | 83 HCC tissues and paired ANTs | Its low expression is related with low OS. | correlated with OS | an independent prognostic factor for OS | (279) |
| JPX | 68 HCC tissues and paired ANTs, plasma samples from 42 patients and 68 healthy controls | Its low expression is related with low OS. | correlated with OS | an independent prognostic factor for OS | (280) |
| XIST | 68 HCC tissues and paired ANTs, plasma samples from 42 patients and 68 healthy controls | Its low expression is related with low OS. | correlated with OS | an independent prognostic factor for OS | |
| GMDS-DT | 198 HCC tissues and paired ANTs | Its low expression is related with low DFS and OS. | – | an independent prognostic factor for DFS and OS | (281) |
| X91348 | 107 HCC tissues and paired ANTs, serum samples from 107 HCC patien6ts and 82 healthy controls | Its low expression is related with low OS. | – | an independent prognostic factor for OS | (282) |
| TCONS_00027978 | 241 HCC tissues and paired ANTs | Its low expression is related with low DFS and OS. | – | an independent prognostic factor for DFS and OS | (283) |
Prognostic role of lncRNAs in HCC (ANT, adjacent non-cancerous tissue; OS, overall survival; RFS, relapse-free survival; DFS, disease-free survival; PFS, progression-free survival; TTR, time to tumor recurrence).
Expression levels of lncRNAs can differentiate HCC tissues from non-tumoral tissues indicating the role of these transcripts as diagnostic biomarkers for HCC. The best diagnostic power values have been reported for NEAT1, PANDAR, CCHE1 and SNHG1. Most notably, serum or plasma levels of a number of lncRNAs such as LINC-ITGB1, LINC00978, LncDQ, PAPAS, MEG3, UCA1 and NEAT1 could be used as diagnostic markers for this kind of cancer (Table 4).
Table 4
| lncRNA | Expression pattern | Sample | Type of biomarker | ROC curve analysis | Reference | ||
|---|---|---|---|---|---|---|---|
| Sensitivity | Specificity | Area under ROC curves (AUC) | |||||
| MALAT1 | Upregulated | Tissue samples | Diagnostic biomarker | – | – | 0.76 | () |
| LINC-ITGB1 | Upregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC from controls) | – | – | 0.8520 | (91) |
| PANDAR | Upregulated | Tissue samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.9564 | (122) |
| LINC00978 | Upregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | 76% | 96% | 0.910 | (155) |
| CCHE1 | Upregulated | Tissue sample | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.9262 | (175) |
| LncDQ | Upregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | 72% | 80% | 0.804 | (204) |
| LINC00963 | Upregulated | Tissue samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.763 | (205) |
| PAPAS | Upregulated | Plasma samples | Diagnostic biomarker (diagnosis of Stage I HCC patients from healthy controls) | – | – | 0.88 | (214) |
| MEG3 | Downregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.8865 | (240) |
| FAM99B | Downregulated | Tissue samples | Diagnostic biomarker (diagnosis HCC from controls) | 70.0% | 63.7% | 0.707 | (268) |
| UCA1 | Upregulated | Serum samples | Diagnostic biomarker (discriminating HCC patients from healthy controls) | 73.3% | 99.0% | 0.902 | (275) |
| Diagnostic biomarker (discriminating HCC patients from benign liver disease patients) | 71.4% | 94.3% | 0.848 | ||||
| JPX | Downregulated | Plasma samples | Diagnostic biomarker (diagnosis of HCC) | 100% | 52.4% | 0.814 | (280) |
| X91348 | Downregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | 82% | 75.4% | 0.807 | (282) |
| MSC-AS1 POLR2J4 EIF3J-AS1 SERHL RMST PVT1 | Upregulated Upregulated Upregulated Upregulated Upregulated Upregulated | Tissue samples | Diagnostic biomarker (tumor vs. non-tumor) | – | – | 0.932 | (284) |
| CASC2 TUG1 | Downregulated Upregulated | Blood samples | Diagnostic biomarker (detection of HCC/HCV from HCV and healthy control group) | 96.6% | 72.5% | – | (285) |
| CASC2 | Downregulated | Blood samples | Diagnostic biomarker (detection of HCC/HCV from HCV and healthy control group) | 67% | 78% | – | |
| TUG1 | Upregulated | Blood samples | Diagnostic biomarker (detection of HCC/HCV from HCV and healthy control group) | 93.3% | 100% | – | |
| AC015908.3 AC091057.3 TMCC1-AS1 DCST1-AS1 FOXD2-AS1 | – – – – – | Tissue samples | Prognostic biomarker (for OS) | – | – | 0.769 | (286) |
| NEAT1 | Upregulated | Serum samples | Diagnostic biomarker (diagnosis HCC from controls) | 100%, | 88.9% | 0.981 | (287) |
| NEAT1 | Upregulated | Tissue samples | Diagnostic biomarker (diagnosis HCC from controls) | – | – | 0.594 | (288) |
| Prognostic biomarker (prediction of capsule or infiltration) | – | – | 0.687 | ||||
| Prognostic biomarker (prediction of tumor node) | – | – | 0.629 | ||||
| Prognostic biomarker (metastasis) | – | – | 0.73 | ||||
| Prognostic biomarker (portal vein tumor embolus) | – | – | 0.656 | ||||
| Prognostic biomarker (vaso-invasion) | – | – | 0.703 | ||||
| GAS5-AS1 | Downregulated | Tissue samples | Diagnostic biomarker (distinguishing HCC from the cirrhosis) | – | – | 0.824 | (279) |
| RP11-160H22.5 XLOC_014172 LOC149086 | Upregulated Upregulated Upregulated | Plasma samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.896 | (289) |
| Prognostic biomarker (prediction of metastasis) | – | – | 0.934 | ||||
| Risk score: MIR100HG SERHL CTD-2574D22.4 SNHG20 | – – – – – | Tissue samples (sequencing data downloaded from TCGA) | Prognostic biomarkers (for OS) | – | – | 0.73 | (290) |
| ENSG00000258332.1 | Upregulated | Serum exosomes | Diagnostic biomarker (discrimination of HCC from chronic hepatitis B) | – | – | 0.719 | (291) |
| LINC00635 | Upregulated | Serum exosomes | Diagnostic biomarker (discrimination of HCC from chronic hepatitis B) | – | – | 0.750 | |
| ENSG00000258332.1 LINC00635 Along with serum AFP | Upregulated Upregulated – – | Serum exosomes | Diagnostic biomarker (discrimination of HCC from chronic hepatitis B) | – | – | 0.894 | |
| lncRNA-D16366 | Downregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | 65.5% | 84.6% | 0.752 | (292) |
| lncRNA-TSIX | Upregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | 87.7%t | 72.7% | 0.866 | (293) |
| CASC9 | Upregulated | Serum samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.933 | (294) |
| ZFAS1 | Upregulated | Plasma samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.801 | (295) |
| lncRNA p34822 | Upregulated | Plasma samples | Diagnostic biomarker (diagnosis of HCC) | 80.9% | 75.8% | 0.845 | (296) |
| Lnc-PCDH9-13:1 | Upregulated | Salivary samples | Diagnostic biomarker (diagnosis of HCC from healthy controls) | 85% | 98% | 0.898 | (297) |
| Diagnostic biomarker (diagnosis of HCC from inactive HBsAg carriers) | 87% | 98% | 0.897 | ||||
| Diagnostic biomarker (diagnosis of HCC from chronic hepatitis B patients) | 87% | 98% | 0.896 | ||||
| Diagnostic biomarker (diagnosis of HCC from liver cirrhosis patients) | 87% | 92% | 0.881 | ||||
| SNHG18 | Downregulated | Plasma samples | Diagnostic biomarker (diagnosis of HCC from healthy controls with α-fetoprotein levels below 200 ng/m) | 75.61% | 73.49% | – | (298) |
| SNHG1 | Upregulated | Plasma samples | Diagnostic biomarker (diagnosis of HCC from healthy controls) | – | – | 0.92 | (299) |
| CTC-297N7.9 | Downregulated | Tissue samples | Diagnostic biomarker (diagnosis of HCC) | – | – | 0.73 | (300) |
| LncRNA-AF085935 | Upregulated | Serum samples | Diagnostic biomarker (discrimination of HBV -positive HCC from healthy controls) | – | – | 0.988 | (301) |
| Diagnostic biomarker (discrimination of HBV patients from healthy controls) | – | – | 0.664 | ||||
| Diagnostic biomarker (discrimination of HBV-positive HCC from HBV patients) | – | – | 0.955 | ||||
| lncRNA-uc003wbd | Upregulated | Serum samples | Diagnostic biomarker (discrimination of HBV -positive HCC from healthy controls) | – | – | 0.994 | |
| Diagnostic biomarker (discrimination of HBV patients from healthy controls) | – | – | 0.982 | ||||
| Diagnostic biomarker (discrimination of HBV-positive HCC from HBV patients) | – | – | 0.810 | ||||
Diagnostic role of lncRNAs in HCC.
Genomic Variants Within lncRNAs and Risk of HCC
Genetic polymorphisms include at least four type of variations namely, single nucleotide polymorphisms, small insertion/deletion polymorphisms, polymorphic repetitive elements and microsatellites. The importance of somatic copy number variations (SCNVs) loci in non-coding regions in the development of HCC has been assessed by Zhou et al. Such investigation has led to identification of recurrent deletion of lncRNA-PRAL in HCC samples in association with poor clinical outcome (224). The lncRNA TSLNC8 on 8p12 is another tumor suppressor lncRNA which is commonly deleted in HCC tissues (226). Table 5 shows the summarized results of studies which assessed association between lncRNAs insertion/deletion or tetranucleotide repeat polymorphisms and HCC.
Table 5
| lncRNA | Polymorphism type | Identifier | Samples | Association with HCC | Association with patient outcome | Functional experiments | Reference |
|---|---|---|---|---|---|---|---|
| GAS5 | Indel polymorphism | rs145204276 | 1034 HCC patients and 1054 controls | Deletion allele is associated with increased risk of HCC. | Deletion allele is correlated with higher expression of GAS5 in HCC tissues. | Genotypes of this polymorphism are associated with methylation status of GAS5 promoter region. | (302) |
| KCNQ1OT1 | Tetranucleotide repeat polymorphism (STR) | rs35622507 | 510 HCC patients and 1014 age and sex matched healthy controls | Heterozygote subjects with one allele 10 and those without allele 10 compared with subjects with homozygote 10–10 genotype have decreased risk of HCC. | – | Cell lines without allele 10 have higher expression of KCNQ1OT1. | (303) |
Association between lncRNAs polymorphisms and HCC.
Discussion
LncRNAs contribute in the pathogenesis of HCC through diverse mechanisms including modulation of oncogenes and tumor suppressor genes as well as modification of tumor microenvironment. The latter route of action has been best exemplified by the lnc-EGFR which enhances differentiation of Tregs therefore increasing immune evasion (). Moreover, certain lncRNAs such as MUF and SNHG7 facilitate EMT process through modulation of Wnt/β-catenin signaling pathway (, 114). Other lncRNAs can modulate EMT through sponging a number of miRNAs. MAPK, PI3K/AKT and JAK/STAT signaling pathways are other cancer-related pathways that are modulated by several lncRNAs in HCC. The interactions between lncRNAs, miRNAs and mRNAs have functional importance in the pathogenesis of HCC. Examples of such trios include H19/miR-15b/CDC42, H19/miR-326/TWIST1, NEAT1/miR-485/STAT3, MALAT1/miR-124-3p/Slug, MALAT1/miR-195/EGFR, MALAT1/miR-22/SNAI1 and ANRIL/miR-144/PBX3.
Functional roles of lncRNAs in HCC have been appraised in animal models. These models have facilitated identification of lncRNAs targets and related pathways (304), which can be used as therapeutic candidates in HCC. HCC-associated lncRNAs can affect gene expression via recruiting epigenetic factors (305), regulation of transcription factors (306), modulation of protein degradation (307) and alteration of phosphorylation of proteins (308).
Genomic alterations and polymorphisms within lncRNA-coding regions have been shown to confer risk of HCC. Such variations might also predict survival of these patients. However, the observed association between these variants and HCC should be verified in independent samples from different ethnic groups. Integration of the results of genome-wide association studies with high throughput sequencing data obtained from microarray and RNA seq experiments would help in discovery of HCC-related single nucleotide polymorphisms within lncRNAs.
The biomarker role of lncRNAs in HCC has been verified by several studies indicating their importance both in the diagnosis and in the prognosis of this cancer. Expression levels of lncRNAs can differentiate HCC patients from inactive HBs Ag carriers, patients with chronic hepatitis and those with liver cirrhosis. In addition, the high diagnostic power values of peripheral levels of a number of lncRNAs such as UCA1 and NEAT1 have potentiated them as methods for non-invasive diagnosis of HCC. Moreover, lncRNAs can be regarded as therapeutic targets in HCC. The importance of lncRNAs as therapeutic targets in HCC has been noted by several experiments in animal models of HCC. Yet, such experiments wait approval in clinical settings. In vivo delivery of a number of lncRNAs such as lncRNA-PRAN, uc.134 and TSLNC8 has been shown to attenuate tumor growth and enhance lifespan of xenograft models of HCC (223, 224, 226). Moreover, a number of lncRNAs such as HULC confer resistance to chemotherapeutic agents (), indicating the potential of targeted therapies against these transcripts in enhancement of response of HCC patients to conventional therapeutic options. Antisense oligonucleotides and small interfering RNAs are putative methods for suppression of expression of lncRNAs (309, 310) whose efficacies have been verified in animal models and cell line experiments. Yet, this knowledge has not been translated into clinical practice.
Taken together, lncRNAs as important class of regulatory transcripts can influence pathogenesis of HCC from different aspects and can be used as suitable markers for differentiation of HCC from related pathogenic conditions.
Statements
Author contributions
SG-F and MT wrote the draft and revised it. BH and MG designed the tables and figures. All authors contributed to the article and approved the submitted version.
Conflict of interest
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.
References
1
BrayFFerlayJSoerjomataramISiegelRLTorreLAJemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin (2018) 68(6):394–424. doi: 10.3322/caac.21492
2
LondonWTMcGlynnKSchottenfeldDFraumeniJ. Cancer epidemiology and prevention. Cancer Epidemiology and Prevention. 3rd edition. In: SchottenfeldDFraumeniJRJF, editors. New York, NY: Oxford University Press (2006) p. 763–86.
3
ZhangDYFriedmanSL. Fibrosis-dependent mechanisms of hepatocarcinogenesis. Hepatology (2012) 56(2):769–75. doi: 10.1002/hep.25670
4
GhouriYAMianIRoweJH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog (2017) 16:1–. doi: 10.4103/jcar.JCar_9_16
5
El–SeragHBRudolphKL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology (2007) 132(7):2557–76. doi: 10.1053/j.gastro.2007.04.061
6
TohTBLimJJChowEK-H. Epigenetics of hepatocellular carcinoma. Clin Transl Med (2019) 8(1):13–. doi: 10.1186/s40169-019-0230-0
7
LongYWangXYoumansDTCechTR. How do lncRNAs regulate transcription? Sci Adv (2017) 3(9):eaao2110–eaao. doi: 10.1126/sciadv.aao2110
8
GuttmanMAmitIGarberMFrenchCLinMFFeldserDet al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature (2009) 458(7235):223–7. doi: 10.1038/nature07672
9
ChoiS-WKimH-WNamJ-W. The small peptide world in long noncoding RNAs. Brief Bioinform (2019) 20(5):1853–64. doi: 10.1093/bib/bby055
10
MaiHZhouBLiuLYangFConranCJiYet al. Molecular pattern of lncRNAs in hepatocellular carcinoma. J Exp Clin Cancer Res (2019) 38(1):198–. doi: 10.1186/s13046-019-1213-0
11
LiZZhangJLiuXLiSWangQDiCet al. The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma. Nat Commun (2018) 9(1):1572. doi: 10.1038/s41467-018-04006-0
12
JiangRTangJChenYDengLJiJXieYet al. The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion. Nat Commun (2017) 8:15129. doi: 10.1038/ncomms15129
13
LiDLiuXZhouJHuJZhangDLiuJet al. Long noncoding RNA HULC modulates the phosphorylation of YB-1 through serving as a scaffold of extracellular signal-regulated kinase and YB-1 to enhance hepatocarcinogenesis. Hepatology (2017) 65(5):1612–27. doi: 10.1002/hep.29010
14
YanXZhangDWuWWuSQianJHaoYet al. Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA-MUF Interaction with ANXA2 and miR-34a. Cancer Res (2017) 77(23):6704–16. doi: 10.1158/0008-5472.CAN-17-1915
15
JinLHeYTangSHuangS. LncRNA GHET1 predicts poor prognosis in hepatocellular carcinoma and promotes cell proliferation by silencing KLF2. J Cell Physiol (2018) 233(6):4726–34. doi: 10.1002/jcp.26257
16
HouZ-HXuX-WFuX-YZhouL-DLiuS-PTanD-M. Long non-coding RNA MALAT1 promotes angiogenesis and immunosuppressive properties of HCC cells by sponging miR-140. Am J Physiology-Cell Physiol (2020) 318(3):C649–C63. doi: 10.1152/ajpcell.00510.2018
17
HouZXuXZhouLFuXTaoSZhouJet al. The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1. Tumor Biol (2017) 39(7):1010428317718135. doi: 10.1177/1010428317718135
18
PengJWuHZhangHFangSZengRet al. miR-143-3p inhibits proliferation and invasion of hepatocellular carcinoma cells by regulating its target gene FGF1. Clin Trans Oncol (2021) 23:468–480. doi: 10.1007/s12094-020-02440-5
19
PanYTongSCuiRFanJLiuCLinYet al. Long non-coding MALAT1 functions as a competing endogenous RNA to regulate vimentin expression by sponging miR-30a-5p in hepatocellular carcinoma. Cell Physiol Biochem (2018) 50(1):108–20. doi: 10.1159/000493962
20
YaoW-FLiuJ-WHuangD-S. MiR-200a inhibits cell proliferation and EMT by down-regulating the ASPH expression levels and affecting ERK and PI3K/Akt pathways in human hepatoma cells. Am J Trans Res (2018) 10(4):1117.
21
CuiRJFanJLLinYCPanYJLiuCWanJHet al. miR-124-3p availability is antagonized by LncRNA-MALAT1 for Slug-induced tumor metastasis in hepatocellular carcinoma. Cancer Med (2019) 8(14):6358–69. doi: 10.1002/cam4.2482
22
LiuDZhuYPangJWengXFengXGuoY. Knockdown of long non-coding RNA MALAT1 inhibits growth and motility of human hepatoma cells via modulation of miR-195. J Cell Biochem (2018) 119(2):1368–80. doi: 10.1002/jcb.26297
23
ChenSWangGTaoKCaiKWuKYeLet al. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis. Cancer Sci (2020) 111(5):1582. doi: 10.1111/cas.14372
24
LiuXLiangYSongRYangGHanJLanYet al. Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. Mol Cancer (2018) 17(1):1–18. doi: 10.1186/s12943-018-0838-5
25
FangLSunJPanZSongYZhongLZhangYet al. Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-IκB. Am J Physiology-Gastrointestinal Liver Physiol (2017) 313(2):G150–G6. doi: 10.1152/ajpgi.00426.2016
26
ZhangXNZhouJLuXJ. The long noncoding RNA NEAT1 contributes to hepatocellular carcinoma development by sponging miR-485 and enhancing the expression of the STAT3. J Cell Physiol (2018) 233(9):6733–41. doi: 10.1002/jcp.26371
27
LiuZChangQYangFLiuBYaoH-WBaiZ-Get al. Long non-coding RNA NEAT1 overexpression is associated with unfavorable prognosis in patients with hepatocellular carcinoma after hepatectomy: A Chinese population-based study. Eur J Surg Oncol (2017) 43(9):1697–703. doi: 10.1016/j.ejso.2017.06.013
28
WangZZouQSongMChenJ. NEAT1 promotes cell proliferation and invasion in hepatocellular carcinoma by negative regulating miR-613 expression. Biomed Pharmacother (2017) 94:612–8. doi: 10.1016/j.biopha.2017.07.111
29
TuJZhaoZXuMLuXChangLJiJ. NEAT1 upregulates TGF-β1 to induce hepatocellular carcinoma progression by sponging hsa-mir-139-5p. J Cell Physiol (2018) 233(11):8578–87. doi: 10.1002/jcp.26524
30
ChenXZhangN. Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR-101-3p/WEE1 axis. Cell Biol Int (2019) 43(1):44–55. doi: 10.1002/cbin.11077
31
HuangJ-LCaoS-wOuQ-sYangBZhengS-hTangJet al. The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma. Mol Cancer (2018) 17(1):1–16. doi: 10.1186/s12943-018-0841-x
32
ZhouQZhangWWangZLiuS. Long non-coding RNA PTTG3P functions as an oncogene by sponging miR-383 and up-regulating CCND1 and PARP2 in hepatocellular carcinoma. BMC Cancer (2019) 19(1):731. doi: 10.1186/s12885-019-5936-2
33
LinJCaoSWangYHuYLiuHLiJet al. Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma. J Exp Clin Cancer Res (2018) 37(1):1–13. doi: 10.1186/s13046-018-0727-1
34
JiDWangYLiHSunBLuoX. Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression. Biochem Biophys Res Commun (2019) 512(2):176–81. doi: 10.1016/j.bbrc.2019.03.049
35
ChenLYaoHWangKLiuX. Long non-coding RNA MALAT1 regulates ZEB1 expression by sponging miR-143-3p and promotes hepatocellular carcinoma progression. J Cell Biochem (2017) 118(12):4836–43. doi: 10.1002/jcb.26158
36
ZhaoZ-BChenFBaiX-F. Long Noncoding RNA MALAT1 regulates hepatocellular carcinoma growth under hypoxia via sponging MicroRNA-200a. Yonsei Med J (2019) 60(8):727–34. doi: 10.3349/ymj.2019.60.8.727
37
JiDWangYSunBYangJLuoX. Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis. Biochem Biophys Res Commun (2019) 513(3):669–74. doi: 10.1016/j.bbrc.2019.04.012
38
WangYYangLChenTLiuXGuoYZhuQet al. A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol Cancer (2019) 18(1):28. doi: 10.1186/s12943-019-0957-7
39
ZhangHLuoCZhangG. LncRNA MCM3AP-AS1 regulates epidermal growth factor receptor and autophagy to promote hepatocellular carcinoma metastasis by interacting with miR-455. DNA Cell Biol (2019) 38(8):857–64. doi: 10.1089/dna.2019.4770
40
HuangM-DChenW-MQiF-ZSunMXuT-PMaPet al. Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2. Mol Cancer (2015) 14(1):165. doi: 10.1186/s12943-015-0431-0
41
LinYHWuMHHuangYHYehCTChengMLChiHCet al. Taurine up-regulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma. Hepatology (2018) 67(1):188–203. doi: 10.1002/hep.29462
42
WangXLiJXuXZhengJLiQ. miR-129 inhibits tumor growth and potentiates chemosensitivity of neuroblastoma by targeting MYO10. Biomed Pharmacother (2018) 103:1312–8. doi: 10.1016/j.biopha.2018.04.153
43
LvJKongYGaoZLiuYZhuPYuZ. LncRNA TUG1 interacting with miR-144 contributes to proliferation, migration and tumorigenesis through activating the JAK2/STAT3 pathway in hepatocellular carcinoma. Int J Biochem Cell Biol (2018) 101:19–28. doi: 10.1016/j.biocel.2018.05.010
44
ChengZLeiZYangPSiAXiangDZhouJet al. Long non-coding RNA THOR promotes cell proliferation and metastasis in hepatocellular carcinoma. Gene (2018) 678:129–36. doi: 10.1016/j.gene.2018.08.035
45
LiKZhaoBWeiDCuiYQianLWangWet al. Long non-coding RNA ANRIL enhances mitochondrial function of hepatocellular carcinoma by regulating the MiR-199a-5p/ARL2 axis. Environ Toxicol (2020) 35(3):313–21. doi: 10.1002/tox.22867
46
HuangDBiCZhaoQDingXBianCWangHet al. Knockdown long non-coding RNA ANRIL inhibits proliferation, migration and invasion of HepG2 cells by down-regulation of miR-191. BMC Cancer (2018) 18(1):1–9. doi: 10.1186/s12885-018-4831-6
47
HuangMChenWQiFXiaRSunMXuTet al. Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell proliferation by epigenetic silencing of KLF2. J Hematol Oncol (2015) 8(1):57–. doi: 10.1186/s13045-015-0153-1
48
MaJLiTHanXYuanH. Knockdown of LncRNA ANRIL suppresses cell proliferation, metastasis, and invasion via regulating miR-122-5p expression in hepatocellular carcinoma. J Cancer Res Clin Oncol (2018) 144(2):205–14. doi: 10.1007/s00432-017-2543-y
49
HuaLWangC-YYaoK-HChenJ-TZhangJ-JMaW-L. High expression of long non-coding RNA ANRIL is associated with poor prognosis in hepatocellular carcinoma. Int J Clin Exp Pathol (2015) 8(3):3076.
50
MaYZhangHLiGHuJLiuXLinL. LncRNA ANRIL promotes cell growth, migration and invasion of hepatocellular carcinoma cells via sponging miR-144. Anti-Cancer Drugs (2019) 30(10):1013–21. doi: 10.1097/CAD.0000000000000807
51
ZhaoXLiuYYuS. Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta (BBA)-Molecular Basis Dis (2017) 1863(7):1805–16. doi: 10.1016/j.bbadis.2017.04.014
52
XuYLuoXHeWChenGLiYLiWet al. Long non-coding RNA PVT1/miR-150/HIG2 axis regulates the proliferation, invasion and the balance of iron metabolism of hepatocellular carcinoma. Cell Physiol Biochem (2018) 49(4):1403–19. doi: 10.1159/000493445
53
LanTYanXLiZXuXMaoQMaWet al. Long non-coding RNA PVT1 serves as a competing endogenous RNA for miR-186-5p to promote the tumorigenesis and metastasis of hepatocellular carcinoma. Tumor Biol (2017) 39(6):1010428317705338. doi: 10.1177/1010428317705338
54
YangLPengXJinHLiuJ. Long non-coding RNA PVT1 promotes autophagy as ceRNA to target ATG3 by sponging microRNA-365 in hepatocellular carcinoma. Gene (2019) 697:94–102. doi: 10.1016/j.gene.2019.02.036
55
HuangDWeiYZhuJWangF. Long non-coding RNA SNHG1 functions as a competitive endogenous RNA to regulate PDCD4 expression by sponging miR-195-5p in hepatocellular carcinoma. Gene (2019) 714:143994. doi: 10.1016/j.gene.2019.143994
56
ZhangMWangWLiTYuXZhuYDingFet al. Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis. Biomed Pharmacother (2016) 80:73–9. doi: 10.1016/j.biopha.2016.02.036
57
ZhangHZhouDYingMChenMChenPChenZet al. Expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) exacerbates hepatocellular carcinoma through suppressing miR-195. Med Sci Monitor: Int Med J Exp Clin Res (2016) 22:4820. doi: 10.12659/MSM.898574
58
ZhaoYKongC-QYeJ-ZBaiTLuoTWangDet al. Upregulation of Long Non-Coding RNA ENST00000429227. 1 Is Correlated with Poor Prognosis in Human Hepatocellular Carcinoma. Med Sci Monitor: Int Med J Exp Clin Res (2019) 25:6539. doi: 10.12659/MSM.916551
59
DingKLiaoYGongDZhaoXJiW. Effect of long non-coding RNA H19 on oxidative stress and chemotherapy resistance of CD133+ cancer stem cells via the MAPK/ERK signaling pathway in hepatocellular carcinoma. Biochem Biophys Res Commun (2018) 502(2):194–201. doi: 10.1016/j.bbrc.2018.05.143
60
ZhouYFanR-GQinC-LJiaJWuX-DZhaW-Z. LncRNA-H19 activates CDC42/PAK1 pathway to promote cell proliferation, migration and invasion by targeting miR-15b in hepatocellular carcinoma. Genomics (2019) 111(6):1862–72. doi: 10.1016/j.ygeno.2018.12.009
61
WeiLQLiLLuCLiuJChenYWuH. Involvement of H19/miR-326 axis in hepatocellular carcinoma development through modulating TWIST1. J Cell Physiol (2019) 234(4):5153–62. doi: 10.1002/jcp.27319
62
XuYZhengYLiuHLiT. Modulation of IGF2BP1 by long non-coding RNA HCG11 suppresses apoptosis of hepatocellular carcinoma cells via MAPK signaling transduction. Int J Oncol (2017) 51(3):791–800. doi: 10.3892/ijo.2017.4066
63
ShanYLiP. Long intergenic non-protein coding RNA 665 regulates viability, apoptosis, and autophagy via the miR-186-5p/MAP4K3 axis in hepatocellular carcinoma. Yonsei Med J (2019) 60(9):842–53. doi: 10.3349/ymj.2019.60.9.842
64
WangHKeJGuoQBarnabo NampoukimeKPYangPMaK. Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK 1 axis. J Cell Mol Med (2018) 22(12):5862–76. doi: 10.1111/jcmm.13856
65
TangQZhengXZhangJ. Long non-coding RNA CRNDE promotes heptaocellular carcinoma cell proliferation by regulating PI3K/Akt/β-catenin signaling. Biomed Pharmacother (2018) 103:1187–93. doi: 10.1016/j.biopha.2018.04.128
66
ZhuLLiuYChenQYuGChenJChenKet al. Long-noncoding RNA colorectal neoplasia differentially expressed gene as a potential target to upregulate the expression of IRX5 by miR-136-5P to promote oncogenic properties in hepatocellular carcinoma. Cell Physiol Biochem (2018) 50(6):2229–48. doi: 10.1159/000495084
67
JiDJiangCZhangLLiangNJiangTYangBet al. LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR-203/BCAT1 axis. J Cell Physiol (2019) 234(5):6548–60. doi: 10.1002/jcp.27396
68
TangDZhaoLPengCRanKMuRAoY. LncRNA CRNDE promotes hepatocellular carcinoma progression by upregulating SIX1 through modulating miR-337-3p. J Cell Biochem (2019) 120(9):16128–42. doi: 10.1002/jcb.28894
69
ChenZZhangZZhaoDFengWMengFHanSet al. Long Noncoding RNA (lncRNA) FOXD2-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Regulating MiR-185/AKT Axis. Med Sci Monitor: Int Med J Exp Clin Res (2019) 25:9618. doi: 10.12659/MSM.918230
70
LeiTZhuXZhuKJiaFLiS. EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/β-catenin signaling pathway. Cancer Biol Ther (2019) 20(7):1007–16. doi: 10.1080/15384047.2019.1595276
71
GaoJYinXYuXDaiCZhouF. Long noncoding RNA LINC00488 functions as a ceRNA to regulate hepatocellular carcinoma cell growth and angiogenesis through miR-330-5. Digestive Liver Dis (2019) 51(7):1050–9. doi: 10.1016/j.dld.2019.03.012
72
KangCLQiBCaiQQFuLSYangYTangCet al. LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics (2019) 9(15):4421. doi: 10.7150/thno.32854
73
ShenYLiuSYuanHYingXFuHZhengX. A long non-coding RNA lncRNA-PE promotes invasion and epithelial–mesenchymal transition in hepatocellular carcinoma through the miR-200a/b-ZEB1 pathway. Tumor Biol (2017) 39(5):1010428317705756. doi: 10.1177/1010428317705756
74
CaoS-QZhengHSunB-CWangZ-LLiuTGuoD-Het al. Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion. World J Gastroenterol (2019) 25(35):5283. doi: 10.3748/wjg.v25.i35.5283
75
XinXWuMMengQWangCLuYYangYet al. Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol Cancer (2018) 17(1):1–16. doi: 10.1186/s12943-018-0843-8
76
BaiRYangQXiRLiLShiDChenK. miR-941 as a promising biomarker for acute coronary syndrome. BMC Cardiovasc Disord (2017) 17(1):227. doi: 10.1186/s12872-017-0653-8
77
LiYLiuGLiXDongHXiaoWLuS. Long non-coding RNA SBF2-AS1 promotes hepatocellular carcinoma progression through regulation of miR-140-5p-TGFBR1 pathway. Biochem Biophys Res Commun (2018) 503(4):2826–32. doi: 10.1016/j.bbrc.2018.08.047
78
ZhangYLiBZhangBMaPWuQMingLet al. LncRNA SBF2-AS1 promotes hepatocellular carcinoma metastasis by regulating EMT and predicts unfavorable prognosis. Eur Rev Med Pharmacol Sci (2018) 22(19):6333–41. doi: 10.26355/eurrev_201810_16044
79
PanYQinTYinSZhangXGaoXMuL. Long non-coding RNA UC001kfo promotes hepatocellular carcinoma proliferation and metastasis by targeting α-SMA. Biomed Pharmacother (2017) 87:669–77. doi: 10.1016/j.biopha.2017.01.018
80
TsangFHAuSLWeiLFanDNLeeJMWongCCet al. Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b. Liver Int (2015) 35(5):1597–606. doi: 10.1111/liv.12746
81
ChangYZhangJZhouCQiuGWangGWangSet al. Long non-coding RNA FOXD2-AS1 plays an oncogenic role in hepatocellular carcinoma by targeting miR−206. Oncol Rep (2018) 40(6):3625–34. doi: 10.3892/or.2018.6752
82
LouYYuYXuXZhouSShenHFanTet al. Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma. J Cell Mol Med (2019) 23(3):1873–84. doi: 10.1111/jcmm.14088
83
HanQChenBZhangKXiaSZhongWZhaoZ. The long non-coding RNA AK001796 contributes to poor prognosis and tumor progression in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2019) 23(5):2013–9. doi: 10.26355/eurrev_201903_17240
84
WangY-DSunX-JYinJ-JYinMWangWNieZ-Qet al. Long non-coding RNA FEZF1-AS1 promotes cell invasion and epithelial-mesenchymal transition through JAK2/STAT3 signaling pathway in human hepatocellular carcinoma. Biomed Pharmacother (2018) 106:134–41. doi: 10.1016/j.biopha.2018.05.116
85
JinXLianJGuanY. Overexpression of long non-coding RNA MINCR contributes to progressive clinicopathological features and poor prognosis of human hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2018) 22(23):8197–202. doi: 10.26355/eurrev_201812_16512
86
CaoJZhangDZengLLiuF. Long noncoding RNA MINCR regulates cellular proliferation, migration, and invasion in hepatocellular carcinoma. Biomed Pharmacother (2018) 102:102–6. doi: 10.1016/j.biopha.2018.03.041
87
ChenTPeiJWangJLuoRLiuLWangLet al. HBx-related long non-coding RNA 01152 promotes cell proliferation and survival by IL-23 in hepatocellular carcinoma. Biomed Pharmacother (2019) 115:108877. doi: 10.1016/j.biopha.2019.108877
88
MoYLuYWangPHuangSHeLLiDet al. Long non-coding RNA XIST promotes cell growth by regulating miR-139-5p/PDK1/AKT axis in hepatocellular carcinoma. Tumor Biol (2017) 39(2):1010428317690999. doi: 10.1177/1010428317690999
89
KongQZhangSLiangCZhangYKongQChenSet al. LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1 expression in hepatocellular carcinoma cell. J Cell Biochem (2018) 119(6):4458–68. doi: 10.1002/jcb.26540
90
XuCHuangQZhangCXuWXuGZhaoXet al. Long non-coding RNA TRPM2-AS as a potential biomarker for hepatocellular carcinoma. Irish J Med Sci (1971-) (2018) 187(3):621–8. doi: 10.1007/s11845-017-1692-y
91
HuangLLiXGaoW. Long non-coding RNA linc-ITGB1 promotes cell proliferation, migration, and invasion in human hepatoma carcinoma by up-regulating ROCK1. Biosci Rep (2018) 38(5). doi: 10.1042/BSR20181289
92
LiOLiZTangQLiYYuanSShenYet al. Long Stress Induced Non-Coding Transcripts 5 (LSINCT5) promotes hepatocellular carcinoma progression through interaction with high-mobility group AT-hook 2 and MiR-4516. Med Sci Monitor: Int Med J Exp Clin Res (2018) 24:8510. doi: 10.12659/MSM.911179
93
YangFJiangYLvL. Long non-coding RNA XLOC_010235 correlates with poor prognosis and promotes tumorigenesis of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2017) 21(21):4867–74.
94
WangCMouLChaiH-XWangFYinY-ZZhangX-Y. Long non-coding RNA HNF1A-AS1 promotes hepatocellular carcinoma cell proliferation by repressing NKD1 and P21 expression. Biomed Pharmacother (2017) 89:926–32. doi: 10.1016/j.biopha.2017.01.031
95
LiuZWeiXZhangALiCBaiJDongJ. Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p. Biochem Biophys Res Commun (2016) 473(4):1268–75. doi: 10.1016/j.bbrc.2016.04.054
96
XuW-HZhangJ-BDangZLiXZhouTLiuJet al. Long non-coding RNA URHC regulates cell proliferation and apoptosis via ZAK through the ERK/MAPK signaling pathway in hepatocellular carcinoma. Int J Biol Sci (2014) 10(7):664. doi: 10.7150/ijbs.8232
97
XiaoJ-NYanT-HYuR-MGaoYZengW-LLuS-Wet al. Long non-coding RNA UCA1 regulates the expression of Snail2 by miR-203 to promote hepatocellular carcinoma progression. J Cancer Res Clin Oncol (2017) 143(6):981–90. doi: 10.1007/s00432-017-2370-1
98
YangJLiJLiuBZhangRGuFZhaoJet al. Long Noncoding RNA AK021443 Promotes Cell Proliferation and Migration by Regulating Epithelial–Mesenchymal Transition in Hepatocellular Carcinoma Cells. DNA Cell Biol (2018) 37(5):481–90. doi: 10.1089/dna.2017.4030
99
TangRWuJZhengLLiZZhouKZhangZet al. Long noncoding RNA RUSC1-AS-N indicates poor prognosis and increases cell viability in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2018) 22(2):388–96. doi: 10.26355/eurrev_201801_14185
100
DouCSunLJinXHanMZhangBLiT. Long non-coding RNA colon cancer–associated transcript 1 functions as a competing endogenous RNA to regulate cyclin-dependent kinase 1 expression by sponging miR-490-3p in hepatocellular carcinoma progression. Tumor Biol (2017) 39(4):1010428317697572. doi: 10.1177/1010428317697572
101
DengLYangS-BXuF-FZhangJ-H. Long noncoding RNA CCAT1 promotes hepatocellular carcinoma progression by functioning as let-7 sponge. J Exp Clin Cancer Res (2015) 34(1):1–10. doi: 10.1186/s13046-015-0136-7
102
GuoJMaYPengXJinHLiuJ. LncRNA CCAT1 promotes autophagy via regulating ATG7 by sponging miR-181 in hepatocellular carcinoma. J Cell Biochem (2019) 120(10):17975–83. doi: 10.1002/jcb.29064
103
ZhangJCaiMJiangDXuL. Upregulated LncRNA-CCAT1 promotes hepatocellular carcinoma progression by functioning as miR-30c-2-3p sponge. Cell Biochem Funct (2019) 37(2):84–92. doi: 10.1002/cbf.3375
104
LiuYWangDLiYYanSDangHYueHet al. Long noncoding RNA CCAT2 promotes hepatocellular carcinoma proliferation and metastasis through up-regulation of NDRG1. Exp Cell Res (2019) 379(1):19–29. doi: 10.1016/j.yexcr.2019.03.029
105
GuoZZhangJFanLLiuJYuHLiXet al. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) predicts poor prognosis and sorafenib resistance in hepatocellular carcinoma. Med Sci Monitor: Int Med J Exp Clin Res (2019) 25:2079. doi: 10.12659/MSM.915541
106
XieXXuXSunCYuZ. Long intergenic noncoding RNA SNHG16 interacts with miR-195 to promote proliferation, invasion and tumorigenesis in hepatocellular carcinoma. Exp Cell Res (2019) 383(1):111501. doi: 10.1016/j.yexcr.2019.111501
107
LanTYuanKYanXXuLLiaoHHaoXet al. LncRNA SNHG10 facilitates hepatocarcinogenesis and metastasis by modulating its homolog SCARNA13 via a positive feedback loop. Cancer Res (2019) 79(13):3220–34. doi: 10.1158/0008-5472.CAN-18-4044
108
LanTMaWHongZWuLChenXYuanY. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res (2017) 36(1):11. doi: 10.1186/s13046-016-0486-9
109
LiuJLuCXiaoMJiangFQuLNiR. Long non-coding RNA SNHG20 predicts a poor prognosis for HCC and promotes cell invasion by regulating the epithelial-to-mesenchymal transition. Biomed Pharmacother (2017) 89:857–63. doi: 10.1016/j.biopha.2017.01.011
110
LiYGuoDZhaoYRenMLuGWangYet al. Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway. Cell Death Dis (2018) 9(9):1–15. doi: 10.1038/s41419-018-0882-5
111
ChenSXieCHuX. lncRNA SNHG6 functions as a ceRNA to up-regulate c-Myc expression via sponging let-7c-5p in hepatocellular carcinoma. Biochem Biophys Res Commun (2019) 519(4):901–8. doi: 10.1016/j.bbrc.2019.09.091
112
WuGJuXWangYLiZGanX. Up-regulation of SNHG6 activates SERPINH1 expression by competitive binding to miR-139-5p to promote hepatocellular carcinoma progression. Cell Cycle (2019) 18(16):1849–67. doi: 10.1080/15384101.2019.1629772
113
CaoCZhangTZhangDXieLZouXLeiLet al. The long non-coding RNA, SNHG6-003, functions as a competing endogenous RNA to promote the progression of hepatocellular carcinoma. Oncogene (2017) 36(8):1112–22. doi: 10.1038/onc.2016.278
114
YaoXLiuCLiuCXiWSunSGaoZ. lncRNA SNHG7 sponges miR-425 to promote proliferation, migration, and invasion of hepatic carcinoma cells via Wnt/β-catenin/EMT signalling pathway. Cell Biochem Funct (2019) 37(7):525–33. doi: 10.1002/cbf.3429
115
YangXSunLWangLYaoBMoHYangW. LncRNA SNHG7 accelerates the proliferation, migration and invasion of hepatocellular carcinoma cells via regulating miR-122-5p and RPL4. Biomed Pharmacother (2019) 118:109386. doi: 10.1016/j.biopha.2019.109386
116
DongJTengFGuoWYangJDingGFuZ. lncRNA SNHG8 promotes the tumorigenesis and metastasis by sponging miR-149-5p and predicts tumor recurrence in hepatocellular carcinoma. Cell Physiol Biochem (2018) 51(5):2262–74. doi: 10.1159/000495871
117
DaiWDaiJ-LTangM-HYeM-SFangS. lncRNA-SNHG15 accelerates the development of hepatocellular carcinoma by targeting miR-490-3p/histone deacetylase 2 axis. World J Gastroenterol (2019) 25(38):5789–99. doi: 10.3748/wjg.v25.i38.5789
118
LiuYYangYWangTWangLWangXLiTet al. Long non-coding RNA CCAL promotes hepatocellular carcinoma progression by regulating AP-2α and Wnt/β-catenin pathway. Int J Biol Macromol (2018) 109:424–34. doi: 10.1016/j.ijbiomac.2017.12.110
119
ShiX-MTengF. Up-regulation of long non-coding RNA Sox2ot promotes hepatocellular carcinoma cell metastasis and correlates with poor prognosis. Int J Clin Exp Pathol (2015) 8(4):4008.
120
ZhouMZhangX-YYuX. Overexpression of the long non-coding RNA SPRY4-IT1 promotes tumor cell proliferation and invasion by activating EZH2 in hepatocellular carcinoma. Biomed Pharmacother (2017) 85:348–54. doi: 10.1016/j.biopha.2016.11.035
121
FuLChenQYaoTLiTYingSHuYet al. Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is used as a novel biomarker for hepatocellular carcinoma. Oncotarget (2017) 8(27):43878. doi: 10.18632/oncotarget.16709
122
PengWFanH. Long non-coding RNA PANDAR correlates with poor prognosis and promotes tumorigenesis in hepatocellular carcinoma. Biomed Pharmacother (2015) 72:113–8. doi: 10.1016/j.biopha.2015.04.014
123
ChenYShenZZhiYZhouHZhangKWangTet al. Long non-coding RNA ROR promotes radioresistance in hepatocelluar carcinoma cells by acting as a ceRNA for microRNA-145 to regulate RAD18 expression. Arch Biochem Biophysics (2018) 645:117–25. doi: 10.1016/j.abb.2018.03.018
124
WangFXieCZhaoWDengZYangHFangQ. Long non-coding RNA CARLo-5 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Clin Exp Med (2017) 17(1):33–43. doi: 10.1007/s10238-015-0395-9
125
WuFLiJDuXZhangWLeiPZhangQ. Long non−coding RNA AB019562 promotes cell proliferation and metastasis in human hepatocellular carcinoma. Mol Med Rep (2017) 16(1):69–74. doi: 10.3892/mmr.2017.6612
126
DongLNiJHuWYuCLiH. Upregulation of long non-coding RNA PlncRNA-1 promotes metastasis and induces epithelial-mesenchymal transition in hepatocellular carcinoma. Cell Physiol Biochem (2016) 38(2):836–46. doi: 10.1159/000443038
127
LiuJWangZYinYLiNYeNBaoBet al. Long noncoding RNA TPTE2P1 promotes the migration and invasion of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2019) 23(9):3733–41. doi: 10.26355/eurrev_201905_17799
128
WenJXuJSunQXingCYinW. Upregulation of long non coding RNA PCAT-1 contributes to cell proliferation, migration and apoptosis in hepatocellular carcinoma. Mol Med Rep (2016) 13(5):4481–6. doi: 10.3892/mmr.2016.5075
129
WangYHuYWuGYangYTangYZhangWet al. Long noncoding RNA PCAT-14 induces proliferation and invasion by hepatocellular carcinoma cells by inducing methylation of miR-372. Oncotarget (2017) 8(21):34429. doi: 10.18632/oncotarget.16260
130
PengYLengWDuanSHongM. Long noncoding RNA BLACAT1 is overexpressed in hepatocellular carcinoma and its downregulation suppressed cancer cell development through endogenously competing against hsa-miR-485-5p. Biomed Pharmacother (2019) 116:109027. doi: 10.1016/j.biopha.2019.109027
131
ZhangLHeXJinTGangLJinZ. Long non-coding RNA DLX6-AS1 aggravates hepatocellular carcinoma carcinogenesis by modulating miR-203a/MMP-2 pathway. Biomed Pharmacother (2017) 96:884–91. doi: 10.1016/j.biopha.2017.10.056
132
KooJILeeH-JJungJHImEKimJ-HShinNet al. The Pivotal Role of Long Noncoding RNA RAB5IF in the Proliferation of Hepatocellular Carcinoma via LGR5 Mediated β-Catenin and c-Myc Signaling. Biomolecules (2019) 9(11):718. doi: 10.3390/biom9110718
133
XuJ-HChangW-HFuH-WShuW-QYuanTChenP. Upregulated long non-coding RNA LOC90784 promotes cell proliferation and invasion and is associated with poor clinical features in HCC. Biochem Biophys Res Commun (2017) 490(3):920–6. doi: 10.1016/j.bbrc.2017.06.141
134
DingCChengSYangZLvZXiaoHDuCet al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci (2014) 15(3):4060–76. doi: 10.3390/ijms15034060
135
ChengDDengJZhangBHeXMengZLiGet al. LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation. EBioMedicine (2018) 36:159–70. doi: 10.1016/j.ebiom.2018.08.055
136
WangWChenGWangBYuanZLiuGNiuBet al. Long non-coding RNA BZRAP1-AS1 silencing suppresses tumor angiogenesis in hepatocellular carcinoma by mediating THBS1 methylation. J Trans Med (2019) 17(1):1–15. doi: 10.1186/s12967-019-02145-6
137
LiYGuoDRenMZhaoYWangXChenYet al. Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway. J Cell Mol Med (2019) 23(9):6271–82. doi: 10.1111/jcmm.14513
138
LiSHuangYHuangYFuYTangDKangRet al. The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation. J Exp Clin Cancer Res (2017) 36(1):1–12. doi: 10.1186/s13046-017-0519-z
139
SongWZhangJXiaQSunM. Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway. Cell Cycle (2019) 18(22):3177–88. doi: 10.1080/15384101.2019.1671089
140
XiaoJLvYJinFLiuYMaYXiongYet al. LncRNA HANR promotes tumorigenesis and increase of chemoresistance in hepatocellular carcinoma. Cell Physiol Biochem (2017) 43(5):1926–38. doi: 10.1159/000484116
141
HuangXGaoYQinJLuS. lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214. Am J Physiology-Gastrointestinal Liver Physiol (2018) 314(5):G559–G65. doi: 10.1152/ajpgi.00242.2017
142
ZhaoLHuKCaoJWangPLiJZengKet al. lncRNA miat functions as a ceRNA to upregulate sirt1 by sponging miR-22-3p in HCC cellular senescence. Aging (Albany NY) (2019) 11(17):7098. doi: 10.18632/aging.102240
143
LiBMaoRLiuCZhangWTangYGuoZ. LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. Life Sci (2018) 197:122–9. doi: 10.1016/j.lfs.2018.02.006
144
HuangYXiangBLiuYWangYKanH. LncRNA CDKN2B-AS1 promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis. Cancer Lett (2018) 437:56–66. doi: 10.1016/j.canlet.2018.08.024
145
ZhuangHCaoGKouCLiD. Overexpressed lncRNA CDKN2B-AS1 is an independent prognostic factor for liver cancer and promotes its proliferation. J BU ON (2019) 24(4):1441–8.
146
ChenJHuangXWangWXieHLiJHuZet al. LncRNA CDKN2BAS predicts poor prognosis in patients with hepatocellular carcinoma and promotes metastasis via the miR-153-5p/ARHGAP18 signaling axis. Aging (Albany NY) (2018) 10(11):3371. doi: 10.18632/aging.101645
147
PanWLiWZhaoJHuangZZhaoJChenSet al. lnc RNA-PDPK 2P promotes hepatocellular carcinoma progression through the PDK 1/AKT/Caspase 3 pathway. Mol Oncol (2019) 13(10):2246–58. doi: 10.1002/1878-0261.12553
148
LiXZhaoQQiJWangWZhangDLiZet al. lncRNA Ftx promotes aerobic glycolysis and tumor progression through the PPARγ pathway in hepatocellular carcinoma. Int J Oncol (2018) 53(2):551–66. doi: 10.3892/ijo.2018.4418
149
KongQLiangCJinYPanYTongDKongQet al. The lncRNA MIR4435-2HG is upregulated in hepatocellular carcinoma and promotes cancer cell proliferation by upregulating miRNA-487a. Cell Mol Biol Lett (2019) 24(1):26. doi: 10.1186/s11658-019-0148-y
150
ZhangWWuYHouBWangYDengDFuZet al. A SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/β-catenin pathway. Mol Oncol (2019) 13(10):2194–210. doi: 10.1002/1878-0261.12560
151
WangHLiangLDongQHuanLHeJLiBet al. Long noncoding RNA miR503HG, a prognostic indicator, inhibits tumor metastasis by regulating the HNRNPA2B1/NF-κB pathway in hepatocellular carcinoma. Theranostics (2018) 8(10):2814. doi: 10.7150/thno.23012
152
ZhangW-LZhaoY-NShiZ-ZGuG-YCongDWeiCet al. HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2. Hum Cell (2019) 32(4):504–14. doi: 10.1007/s13577-019-00269-x
153
ZhangYXuJZhangSAnJZhangJHuangJet al. HOXA-AS2 promotes proliferation and induces epithelial-mesenchymal transition via the miR-520c-3p/GPC3 axis in hepatocellular carcinoma. Cell Physiol Biochem (2018) 50(6):2124–38. doi: 10.1159/000495056
154
ZhangXChenHZhouBZhangQLiaoYWangJet al. lncRNA HOXB-AS3 promotes hepatoma by inhibiting p53 expression. Eur Rev Med Pharmacol Sci (2018) 22(20):6784–92. doi: 10.26355/eurrev_201810_16145
155
XuXGuJDingXGeGZangXJiRet al. LINC00978 promotes the progression of hepatocellular carcinoma by regulating EZH2-mediated silencing of p21 and E-cadherin expression. Cell Death Dis (2019) 10(10):1–15. doi: 10.1038/s41419-019-1990-6
156
WangC-ZYanG-XDongD-SXinHLiuZ-Y. LncRNA-ATB promotes autophagy by activating Yes-associated protein and inducing autophagy-related protein 5 expression in hepatocellular carcinoma. World J Gastroenterol (2019) 25(35):5310. doi: 10.3748/wjg.v25.i35.5310
157
HuangHChenJDingCMJinXJiaZMPengJ. Lnc RNA NR 2F1-AS 1 regulates hepatocellular carcinoma oxaliplatin resistance by targeting ABCC 1 via miR-363. J Cell Mol Med (2018) 22(6):3238–45. doi: 10.1111/jcmm.13605
158
GuoDLiYChenYZhangDWangXLuGet al. DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway. Cell Proliferation (2019) 52(4):e12628. doi: 10.1111/cpr.12628
159
WangJPuJZhangYYaoTLuoZLiWet al. DANCR contributed to hepatocellular carcinoma malignancy via sponging miR-216a-5p and modulating KLF12. J Cell Physiol (2019) 234(6):9408–16. doi: 10.1002/jcp.27625
160
ZhangLWangYSunJMaHGuoC. LINC00205 promotes proliferation, migration and invasion of HCC cells by targeting miR-122-5p. Pathology-Research Pract (2019) 215(9):152515. doi: 10.1016/j.prp.2019.152515
161
FanJZhangJHuangSLiP. lncRNA OSER1-AS1 acts as a ceRNA to promote tumorigenesis in hepatocellular carcinoma by regulating miR-372-3p/Rab23 axis. Biochem Biophys Res Commun (2020) 521(1):196–203. doi: 10.1016/j.bbrc.2019.10.105
162
GuoYBaiMLinLHuangJAnYLiangLet al. LncRNA DLEU2 aggravates the progression of hepatocellular carcinoma through binding to EZH2. Biomed Pharmacother (2019) 118:109272. doi: 10.1016/j.biopha.2019.109272
163
HuangJ-LRenT-YCaoS-WZhengS-HHuX-MHuY-Wet al. HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget (2015) 6(32):33791. doi: 10.18632/oncotarget.5667
164
BaoJChenXHouYKangGLiQXuY. LncRNA DBH-AS1 facilitates the tumorigenesis of hepatocellular carcinoma by targeting miR-138 via FAK/Src/ERK pathway. Biomed Pharmacother (2018) 107:824–33. doi: 10.1016/j.biopha.2018.08.079
165
WangJZhangYLuLLuYTangQPuJ. Insight into the molecular mechanism of LINC00152/miR-215/CDK13 axis in hepatocellular carcinoma progression. J Cell Biochem (2019) 120(11):18816–25. doi: 10.1002/jcb.29197
166
LiS-QChenQQinH-XYuY-QWengJMoQ-Ret al. Long intergenic nonprotein coding RNA 0152 promotes hepatocellular carcinoma progression by regulating phosphatidylinositol 3-Kinase/Akt/Mammalian target of rapamycin signaling pathway through miR-139/PIK3CA. Am J Pathol (2020) 190(5):1095–107. doi: 10.1016/j.ajpath.2019.11.010
167
MaPWangHSunJLiuHZhengCZhouXet al. LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis. Cell Cycle (2018) 17(8):974–84. doi: 10.1080/15384101.2018.1464834
168
LuXZhouCLiRLiangZZhaiWZhaoLet al. Critical role for the long non-coding RNA AFAP1-AS1 in the proliferation and metastasis of hepatocellular carcinoma. Tumor Biol (2016) 37(7):9699–707. doi: 10.1007/s13277-016-4858-8
169
ChenHYangFLiXGongZ-JWangL-W. Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells. Biochem Biophys Res Commun (2018) 499(3):702–10. doi: 10.1016/j.bbrc.2018.03.215
170
LiYLiYXuX. The long noncoding RNA cardiac hypertrophy-related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA-211. J Cell Biochem (2019) 120(8):13361–71. doi: 10.1002/jcb.28611
171
YangXCaiJBPengRWeiCYLuJCGaoCet al. The long noncoding RNA NORAD enhances the TGF-β pathway to promote hepatocellular carcinoma progression by targeting miR-202-5p. J Cell Physiol (2019) 234(7):12051–60. doi: 10.1002/jcp.27869
172
QiHLuYLvJWuHLuJZhangCet al. The long noncoding RNA lncPARP1 contributes to progression of hepatocellular carcinoma through up-regulation of PARP1. Biosci Rep (2018) 38(3):BSR20180703. doi: 10.1042/BSR20180703
173
LiYYeYFengBQiY. Long noncoding RNA lncARSR promotes doxorubicin resistance in hepatocellular carcinoma via modulating PTEN-PI3K/Akt pathway. J Cell Biochem (2017) 118(12):4498–507. doi: 10.1002/jcb.26107
174
ShinVYChenJCheukIW-YSiuM-THoC-WWangXet al. Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death Disease (2019) 10(4):1–10. doi: 10.1038/s41419-019-1513-5
175
PengWFanH. Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway. Biomed Pharmacother (2016) 83:450–5. doi: 10.1016/j.biopha.2016.06.056
176
JinWChenLCaiXZhangYZhangJMaDet al. Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1. Oncol Rep (2017) 37(1):273–80. doi: 10.3892/or.2016.5248
177
SuiC-JZhouY-MShenW-FDaiB-HLuJ-JZhangM-Fet al. Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429. J Mol Med (2016) 94(11):1281–96. doi: 10.1007/s00109-016-1442-z
178
HuangGJiangHLinYWuYCaiWShiBet al. lncAKHE enhances cell growth and migration in hepatocellular carcinoma via activation of NOTCH2 signaling. Cell Death Dis (2018) 9(5):1–11. doi: 10.1038/s41419-018-0554-5
179
RenWGuanWZhangJWangFXuG. Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development. Aging (Albany NY) (2019) 11(7):2151. doi: 10.18632/aging.101908
180
LiTXieJShenCChengDShiYWuZet al. Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene (2016) 35(12):1575–84. doi: 10.1038/onc.2015.223
181
YuJOuZLeiYChenLSuQZhangK. LncRNA MYCNOS facilitates proliferation and invasion in hepatocellular carcinoma by regulating miR-340. Hum Cell (2020) 33(1):148–58. doi: 10.1007/s13577-019-00303-y
182
LiuZWangYWangLYaoBSunLLiuRet al. Long non-coding RNA AGAP2-AS1, functioning as a competitive endogenous RNA, upregulates ANXA11 expression by sponging miR-16-5p and promotes proliferation and metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res (2019) 38(1):194. doi: 10.1186/s13046-019-1188-x
183
TranDKesslerCNiehusSMahnkopfMKochATamuraT. Myc target gene, long intergenic noncoding RNA, Linc00176 in hepatocellular carcinoma regulates cell cycle and cell survival by titrating tumor suppressor microRNAs. Oncogene (2018) 37(1):75–85. doi: 10.1038/onc.2017.312
184
TangYHHeGLHuangSZZhongKBLiaoHCaiLet al. The long noncoding RNA AK002107 negatively modulates miR-140-5p and targets TGFBR1 to induce epithelial–mesenchymal transition in hepatocellular carcinoma. Mol Oncol (2019) 13(5):1296–310. doi: 10.1002/1878-0261.12487
185
LiYZhuangWHuangMLiX. Long noncoding RNA DDX11-AS1 epigenetically represses LATS2 by interacting with EZH2 and DNMT1 in hepatocellular carcinoma. Biochem Biophys Res Commun (2019) 514(4):1051–7. doi: 10.1016/j.bbrc.2019.05.042
186
LuoXZhouNWangLZengQTangH. Long Noncoding RNA GATA3-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Suppression of PTEN, CDKN1A, and TP53. Can J Gastroenterol Hepatol (2019) 2019:1389653. doi: 10.1155/2019/1389653
187
ZhangWLiuSLiuKLiuY. Long non-coding RNA deleted in lymphocytic leukaemia 1 promotes hepatocellular carcinoma progression by sponging miR-133a to regulate IGF-1R expression. J Cell Mol Med (2019) 23(8):5154–64. doi: 10.1111/jcmm.14384
188
XuXYinYTangJXieYHanZZhangXet al. Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification. Cell Death Dis (2017) 8(10):e3124–e. doi: 10.1038/cddis.2017.519
189
TangTGuoCXiaTZhangRZenKPanYet al. LncCCAT1 promotes breast Cancer stem cell function through activating WNT/β-catenin signaling. Theranostics (2019) 9(24):7384. doi: 10.7150/thno.37892
190
XuXLouYTangJTengYZhangZYinYet al. The long non-coding RNA Linc-GALH promotes hepatocellular carcinoma metastasis via epigenetically regulating Gankyrin. Cell Death Dis (2019) 10(2):1–13. doi: 10.1038/s41419-019-1348-0
191
MaMXuHLiuGWuJLiCWangXet al. Metabolism-induced tumor activator 1 (MITA1), an Energy Stress–Inducible Long Noncoding RNA, Promotes Hepatocellular Carcinoma Metastasis. Hepatology (2019) 70(1):215–30. doi: 10.1002/hep.30602
192
WangYLLiuJYYangJEYuXMChenZLChenYJet al. Lnc-UCID promotes G1/S transition and hepatoma growth by preventing DHX9-mediated CDK6 down-regulation. Hepatology (2019) 70(1):259–75. doi: 10.1002/hep.30613
193
YangXYaoBNiuYChenTMoHWangLet al. Hypoxia-induced lncRNA EIF3J-AS1 accelerates hepatocellular carcinoma progression via targeting miR-122–5p/CTNND2 axis. Biochem Biophys Res Commun (2019) 518(2):239–45. doi: 10.1016/j.bbrc.2019.08.039
194
FanHLvPMuTZhaoXLiuYFengYet al. LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells. Cancer Lett (2018) 429:89–99. doi: 10.1016/j.canlet.2018.05.010
195
ZhuangJHeSWangGWangGNiJZhangSet al. Long Noncoding RNA FGFR3-AS1 Promotes Hepatocellular Carcinoma Carcinogenesis via Modulating the PI3K/AKT Pathway. Oncol Res Featuring Preclinical Clin Cancer Ther (2018) 26(8):1257–65. doi: 10.3727/096504018X15172756878992
196
MoJLiBZhouYXuYJiangHChengXet al. LINC00473 promotes hepatocellular carcinoma progression via acting as a ceRNA for microRNA-195 and increasing HMGA2 expression. Biomed Pharmacother (2019) 120:109403. doi: 10.1016/j.biopha.2019.109403
197
GaoJYinXYuXDaiCZhouF. Long noncoding LINC01551 promotes hepatocellular carcinoma cell proliferation, migration, and invasion by acting as a competing endogenous RNA of microRNA-122-5p to regulate ADAM10 expression. J Cell Biochem (2019) 120(10):16393–407. doi: 10.1002/jcb.28549
198
YuSLiNHuangZChenRYiPKangRet al. A novel lncRNA, TCONS_00006195, represses hepatocellular carcinoma progression by inhibiting enzymatic activity of ENO1. Cell Death Dis (2018) 9(12):1–13. doi: 10.1038/s41419-018-1231-4
199
WangRJiangJJiangTWangYChenL. Increased long noncoding RNA LINC00511 is correlated with poor prognosis and contributes to cell proliferation and metastasis by modulating miR-424 in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2019) 23(8):3291–301. doi: 10.26355/eurrev_201904_17691
200
HuW-YWeiH-YLiK-MWangR-BXuX-QFengR. LINC00511 as a ceRNA promotes cell malignant behaviors and correlates with prognosis of hepatocellular carcinoma patients by modulating miR-195/EYA1 axis. Biomed Pharmacother (2020) 121:109642. doi: 10.1016/j.biopha.2019.109642
201
GongJQiXZhangYYuYLinXLiHet al. Long noncoding RNA linc00462 promotes hepatocellular carcinoma progression. Biomed Pharmacother (2017) 93:40–7. doi: 10.1016/j.biopha.2017.06.004
202
ChenZZhouZHeCZhangJWangJXiaoZ. Down-regulation of LncRNA NR027113 inhibits cell proliferation and metastasis via PTEN/PI3K/AKT signaling pathway in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2018) 22(21):7222–32. doi: 10.26355/eurrev_201811_16256
203
ChenZXuDZhangT. Inhibition of proliferation and invasion of hepatocellular carcinoma cells by lncRNA-ASLNC02525 silencing and the mechanism. Int J Oncol (2017) 51(3):851–8. doi: 10.3892/ijo.2017.4069
204
ZengBLinZYeHChengDZhangGZhouJet al. Upregulation of LncDQ is associated with poor prognosis and promotes tumor progression via epigenetic regulation of the EMT pathway in HCC. Cell Physiol Biochem (2018) 46(3):1122–33. doi: 10.1159/000488841
205
WuJTianXAnQGuanXHaoC. LINC00963 promotes hepatocellular carcinoma progression by activating PI3K/AKT pathway. Eur Rev Med Pharmacol Sci (2018) 22(6):1645–52. doi: 10.26355/eurrev_201803_14574
206
ChenJWuDZhangYYangYDuanYAnY. LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma. Clin Sci (2019) 133(2):367–79. doi: 10.1042/CS20180814
207
ChenHLiuJHuGShiLLanT. Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway. Eur Rev Med Pharmacol Sci (2017) 21(15):3412–20.
208
LiuWHuaiRZhangYRaoSDingRMaoCet al. Down-regulation expression of TGFB2-AS1 inhibits the proliferation, migration, invasion and induces apoptosis in HepG2 cells. Genes Genomics (2019) 41(8):951–9. doi: 10.1007/s13258-019-00826-6
209
ZhangKZhaoZYuJChenWXuQChenL. LncRNA FLVCR1-AS1 acts as miR-513c sponge to modulate cancer cell proliferation, migration, and invasion in hepatocellular carcinoma. J Cell Biochem (2018) 119(7):6045–56. doi: 10.1002/jcb.26802
210
TuJZhaoZXuMChenMWengQWangJet al. LINC00707 contributes to hepatocellular carcinoma progression via sponging miR-206 to increase CDK14. J Cell Physiol (2019) 234(7):10615–24. doi: 10.1002/jcp.27737
211
ChenZLiuYYaoLGuoSGaoYZhuP. The long noncoding RNA lncZic2 drives the self-renewal of liver tumor–initiating cells via the protein kinase C substrates MARCKS and MARCKSL1. J Biol Chem (2018) 293(21):7982–92. doi: 10.1074/jbc.RA117.001321
212
LiSSuiMSunZZhangW. LncRNA 00152 promotes the development of hepatocellular carcinoma by activating JAK2/STAT3 pathway. Eur Rev Med Pharmacol Sci (2019) 23(3):1038–46. doi: 10.26355/eurrev_201902_16991
213
LiuLZhuYLiuAFengYChenY. Long noncoding RNA LINC00511 involves in breast cancer recurrence and radioresistance by regulating STXBP4 expression via miR-185. Eur Rev Med Pharmacol Sci (2019) 23(17):7457–68. doi: 10.26355/eurrev_201909_18855
214
MaJQinCYuanZLiuS. LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR-188-5p. J Cell Biochem (2019) 120(8):13494–500. doi: 10.1002/jcb.28623
215
HuangHBuYZZhangXYLiuJZhuLYFangY. LINC01433 promotes hepatocellular carcinoma progression via modulating the miR-1301/STAT3 axis. J Cell Physiol (2019) 234(5):6116–24. doi: 10.1002/jcp.27366
216
SunJZhangYLiBDongYSunCZhangFet al. PITPNA-AS1 abrogates the inhibition of miR-876-5p on WNT5A to facilitate hepatocellular carcinoma progression. Cell Death Dis (2019) 10(11):1–15. doi: 10.1038/s41419-019-2067-2
217
TanNZhuBShuHTaoYFWuJRFangMet al. Effect of lncRNA−BC200 on proliferation and migration of liver cancer cells in vitro and in vivo. Oncol Rep (2020) 43(2):461–70. doi: 10.3892/or.2019.7447
218
HuangWLiuJYanJHuangZZhangXMaoYet al. LncRNA LINC00470 promotes proliferation through association with NF45/NF90 complex in hepatocellular carcinoma. Hum Cell (2020) 33(1):131–9. doi: 10.1007/s13577-019-00288-8
219
García-VenzorAMandujano-TinocoEALizarragaFZampedriCKrötzschESalgadoRMet al. Microenvironment-regulated lncRNA-HAL is able to promote stemness in breast cancer cells. Biochim Biophys Acta (BBA)-Molecular Cell Res (2019) 1866(12):118523. doi: 10.1016/j.bbamcr.2019.118523
220
TuJZhaoZXuMChenMWengQJiJ. LINC00460 promotes hepatocellular carcinoma development through sponging miR-485-5p to up-regulate PAK1. Biomed Pharmacother (2019) 118:109213. doi: 10.1016/j.biopha.2019.109213
221
HuMHanYZhangYZhouYYeL. lncRNA TINCR sponges miR-214-5p to upregulate ROCK1 in hepatocellular carcinoma. BMC Med Genet (2020) 21(1):1–6. doi: 10.1186/s12881-019-0940-6
222
FenHHongminZWeiWChaoYYangYBeiLet al. RHPN1-AS1 drives the progression of hepatocellular carcinoma via regulating miR-596/IGF2BP2 axis. Curr Pharm Des (2019) 25(43):4630–40. doi: 10.2174/1381612825666191105104549
223
NiWZhangYZhanZYeFLiangYHuangJet al. A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1. J Hematol Oncol (2017) 10(1):91. doi: 10.1186/s13045-017-0449-4
224
ZhouCCYangFYuanSXMaJZLiuFYuanJHet al. Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma. Hepatology (2016) 63(3):850–63. doi: 10.1002/hep.28393
225
YangFHuoXSYuanSXZhangLZhouWPWangFet al. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell (2013) 49(6):1083–96. doi: 10.1016/j.molcel.2013.01.010
226
ZhangJLiZLiuLWangQLiSChenDet al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology (2018) 67(1):171–87. doi: 10.1002/hep.29405
227
WangYLiuZYaoBLiQWangLWangCet al. Long non-coding RNA CASC2 suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis. Mol Cancer (2017) 16(1):123. doi: 10.1186/s12943-017-0702-z
228
QinGTuXLiHCaoPChenXSongJet al. Long Noncoding RNA p53-Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma. Hepatology (2020) 71(1):112–29. doi: 10.1002/hep.30793
229
DingHLiuJZouRChengPSuY. Long non-coding RNA TPTEP1 inhibits hepatocellular carcinoma progression by suppressing STAT3 phosphorylation. J Exp Clin Cancer Res (2019) 38(1):189. doi: 10.1186/s13046-019-1193-0
230
SunJLiuLZouHYuW. The Long Non-Coding RNA CASC2 Suppresses Cell Viability, Migration, and Invasion in Hepatocellular Carcinoma Cells by Directly Downregulating miR-183. Yonsei Med J (2019) 60(10):905–13. doi: 10.3349/ymj.2019.60.10.905
231
GanYHanNHeXYuJZhangMZhouYet al. Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma. Tumor Biol (2017) 39(6):1010428317706229. doi: 10.1177/1010428317706229
232
ZhaoLZhangYZhangY. Long noncoding RNA CASC2 regulates hepatocellular carcinoma cell oncogenesis through miR-362-5p/Nf-κB axis. J Cell Physiol (2018) 233(10):6661–70. doi: 10.1002/jcp.26446
233
FanJCZengFLeYGXinL. LncRNA CASC2 inhibited the viability and induced the apoptosis of hepatocellular carcinoma cells through regulating miR-24-3p. J Cell Biochem (2018) 119(8):6391–7. doi: 10.1002/jcb.26479
234
WangY-GWangTShiMZhaiB. Long noncoding RNA EPB41L4A-AS2 inhibits hepatocellular carcinoma development by sponging miR-301a-5p and targeting FOXL1. J Exp Clin Cancer Res (2019) 38(1):1–13. doi: 10.1186/s13046-019-1128-9
235
CaiKLiTGuoLGuoHZhuWYanLet al. Long non-coding RNA LINC00467 regulates hepatocellular carcinoma progression by modulating miR-9-5p/PPARA expression. Open Biol (2019) 9(9):190074. doi: 10.1098/rsob.190074
236
WangXSunWShenWXiaMChenCXiangDet al. Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. J Hepatol (2016) 64(6):1283–94. doi: 10.1016/j.jhep.2016.01.019
237
LiuFYuanJHuangJYangFWangTMaJet al. Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a. Oncogene (2016) 35(41):5422–34. doi: 10.1038/onc.2016.80
238
ChenCZhengQKangWYuC. Long non-coding RNA LINC00472 suppresses hepatocellular carcinoma cell proliferation, migration and invasion through miR-93-5p/PDCD4 pathway. Clinics Res Hepatol Gastroenterol (2019) 43(4):436–45. doi: 10.1016/j.clinre.2018.11.008
239
ZhuPLiYLiPZhangYWangX. c-Myc induced the regulation of long non-coding RNA RHPN1-AS1 on breast cancer cell proliferation via inhibiting P53. Mol Genet Genomics (2019) 294(5):1219–29. doi: 10.1007/s00438-019-01572-w
240
DongHZhangYXuYMaRLiuLLuoCet al. Downregulation of long non-coding RNA MEG3 promotes proliferation, migration, and invasion of human hepatocellular carcinoma cells by upregulating TGF-β1. Acta Biochim Biophys Sinica (2019) 51(6):645–52. doi: 10.1093/abbs/gmz046
241
XuFWangBLiuMLiuTZhangR. A long non-coding RNA TSLD8 inhibits hepatocellular carcinoma by stabilizing WWOX. Biochem Biophys Res Commun (2019) 516(2):526–32. doi: 10.1016/j.bbrc.2019.06.043
242
WuJZhouXFanYChengXLuBChenZ. Long non-coding RNA 00312 downregulates cyclin B1 and inhibits hepatocellular carcinoma cell proliferation in vitro and in vivo. Biochem Biophys Res Commun (2018) 497(1):173–80. doi: 10.1016/j.bbrc.2018.02.049
243
YaoZXiongZLiRLiangHJiaCDengM. Long non-coding RNA NRON is downregulated in HCC and suppresses tumour cell proliferation and metastasis. Biomed Pharmacother (2018) 104:102–9. doi: 10.1016/j.biopha.2018.05.006
244
ChenC-LTsengY-WWuJ-CChenG-YLinK-CHwangS-Met al. Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation. Biomaterials (2015) 44:71–81. doi: 10.1016/j.biomaterials.2014.12.023
245
SunQ-MHuBFuP-YTangW-GZhangXZhanHet al. Long non-coding RNA 00607 as a tumor suppressor by modulating NF-κB p65/p53 signaling axis in hepatocellular carcinoma. Carcinogenesis (2018) 39(12):1438–46. doi: 10.1093/carcin/bgy113
246
WangT-HLinY-SChenYYehC-THuangY-LHsiehT-Het al. Long non-coding RNA AOC4P suppresses hepatocellular carcinoma metastasis by enhancing vimentin degradation and inhibiting epithelial-mesenchymal transition. Oncotarget (2015) 6(27):23342. doi: 10.18632/oncotarget.4344
247
SuiJYangXQiWGuoKGaoZWangLet al. Long non-coding RNA Linc-USP16 functions as a tumour suppressor in hepatocellular carcinoma by regulating PTEN expression. Cell Physiol Biochem (2017) 44(3):1188–98. doi: 10.1159/000485449
248
SunXZhengGLiCLiuC. Long non−coding RNA Fer−1−like family member 4 suppresses hepatocellular carcinoma cell proliferation by regulating PTEN in vitro and in vivo. Mol Med Rep (2019) 19(1):685–92. doi: 10.3892/mmr.2018.9629
249
WuJHuangJWangWXuJYinMChengNet al. Long non-coding RNA Fer-1-like protein 4 acts as a tumor suppressor via miR-106a-5p and predicts good prognosis in hepatocellular carcinoma. Cancer Biomarkers (2017) 20(1):55–65. doi: 10.3233/CBM-170090
250
WangXDongKJinQMaYYinSWangS. Upregulation of lncRNA FER1L4 suppresses the proliferation and migration of the hepatocellular carcinoma via regulating PI3K/AKT signal pathway. J Cell Biochem (2019) 120(4):6781–8. doi: 10.1002/jcb.27980
251
PengCHuWWengXTongRChengSDingCet al. Over expression of long non-coding RNA PANDA promotes hepatocellular carcinoma by inhibiting senescence associated inflammatory factor IL8. Sci Rep (2017) 7(1):1–11. doi: 10.1038/s41598-017-04045-5
252
BoCLiXHeLZhangSLiNAnY. A novel long noncoding RNA HHIP-AS1 suppresses hepatocellular carcinoma progression through stabilizing HHIP mRNA. Biochem Biophys Res Commun (2019) 520(2):333–40. doi: 10.1016/j.bbrc.2019.09.137
253
LinX-QHuangZ-MChenXWuFWuW. XIST induced by JPX suppresses hepatocellular carcinoma by sponging miR-155-5p. Yonsei Med J (2018) 59(7):816–26. doi: 10.3349/ymj.2018.59.7.816
254
ZhangGLiHSunRLiPYangZLiuYet al. Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2. J Cell Mol Med (2019) 23(5):3271–9. doi: 10.1111/jcmm.14213
255
PanWZhangNLiuWLiuJZhouLLiuYet al. The long noncoding RNA GAS8-AS1 suppresses hepatocarcinogenesis by epigenetically activating the tumor suppressor GAS8. J Biol Chem (2018) 293(44):17154–65. doi: 10.1074/jbc.RA118.003055
256
HuBCaiHZhengRYangSZhouZTuJ. Long non-coding RNA 657 suppresses hepatocellular carcinoma cell growth by acting as a molecular sponge of miR-106a-5p to regulate PTEN expression. Int J Biochem Cell Biol (2017) 92:34–42. doi: 10.1016/j.biocel.2017.09.008
257
GaoYWangGZhangCLinMLiuXZengYet al. Long non-coding RNA linc-cdh4-2 inhibits the migration and invasion of HCC cells by targeting R-cadherin pathway. Biochem Biophys Res Commun (2016) 480(3):348–54. doi: 10.1016/j.bbrc.2016.10.048
258
LiYHanXLiQWangCLouZWangX. Long noncoding RNA HOXD-AS1 induces epithelial-mesenchymal transition in breast cancer by acting as a competing endogenous RNA of miR-421. J Cell Biochem (2019) 120(6):10633–42. doi: 10.1002/jcb.28353
259
SunWXuXJiangYJinXZhouPLiuYet al. Transcriptome analysis of luminal breast cancer reveals a role for LOL in tumor progression and tamoxifen resistance. Int J Cancer (2019) 145(3):842–56. doi: 10.1002/ijc.32185
260
ChangLLiCLanTWuLYuanYLiuQet al. Decreased expression of long non-coding RNA GAS5 indicates a poor prognosis and promotes cell proliferation and invasion in hepatocellular carcinoma by regulating vimentin. Mol Med Rep (2016) 13(2):1541–50. doi: 10.3892/mmr.2015.4716
261
HuLYeHHuangGLuoFLiuYLiuYet al. Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21. Tumor Biol (2016) 37(2):2691–702. doi: 10.1007/s13277-015-4111-x
262
ZhaoPCuiXZhaoLLiuLWangD. Overexpression of Growth-Arrest-Specific Transcript 5 Improved Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222. DNA Cell Biol (2020) 39(4):724–32. doi: 10.1089/dna.2019.5282
263
GeZChengZYangXHuoXWangNWangHet al. Long noncoding RNA SchLAH suppresses metastasis of hepatocellular carcinoma through interacting with fused in sarcoma. Cancer Sci (2017) 108(4):653–62. doi: 10.1111/cas.13200
264
YuXTangWYangYTangLDaiRPuBet al. Long noncoding RNA NKILA enhances the anti-cancer effects of baicalein in hepatocellular carcinoma via the regulation of NF-κB signaling. Chem Biol Interactions (2018) 285:48–58. doi: 10.1016/j.cbi.2018.02.027
265
ZhangH-FLiWHanY-D. LINC00261 suppresses cell proliferation, invasion and Notch signaling pathway in hepatocellular carcinoma. Cancer Biomarkers (2018) 21(3):575–82. doi: 10.3233/CBM-170471
266
YanSTangZChenKLiuYYuGChenQet al. Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression. J Exp Clin Cancer Res (2018) 37(1):214. doi: 10.1186/s13046-018-0853-9
267
ZhengY-LLiLJiaY-XZhangB-ZLiJ-CZhuY-Het al. LINC01554-mediated glucose metabolism reprogramming suppresses tumorigenicity in hepatocellular carcinoma via downregulating PKM2 expression and inhibiting Akt/mTOR signaling pathway. Theranostics (2019) 9(3):796. doi: 10.7150/thno.28992
268
MoMLiuSMaXTanCWeiLShengYet al. A liver-specific lncRNA, FAM99B, suppresses hepatocellular carcinoma progression through inhibition of cell proliferation, migration, and invasion. J Cancer Res Clin Oncol (2019) 145(8):2027–38. doi: 10.1007/s00432-019-02954-8
269
ShengNLiYQianRLiY. The clinical significance and biological function of lncRNA RGMB-AS1 in hepatocellular carcinoma. Biomed Pharmacother (2018) 98:577–84. doi: 10.1016/j.biopha.2017.12.067
270
YanSShanXChenKLiuYYuGChenQet al. LINC00052/miR-101-3p axis inhibits cell proliferation and metastasis by targeting SOX9 in hepatocellular carcinoma. Gene (2018) 679:138–49. doi: 10.1016/j.gene.2018.08.038
271
WangYGLiuJShiMChenFX. LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting the miR-346/KLF14 axis. J Cell Physiol (2019) 234(1):572–80. doi: 10.1002/jcp.26779
272
ZhouYHuanLWuYBaoCChenBWangLet al. LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma. Cancer Lett (2020) 469:399–409. doi: 10.1016/j.canlet.2019.11.007
273
DuJChenMLiuJHuPGuanHJiaoX. Lncrna f11-as1 suppresses liver hepatocellular carcinoma progression by competitively binding with mir-3146 to regulate pten expression. J Cell Biochem (2019) 120(10):18457–64. doi: 10.1002/jcb.29163
274
WuJShuangZZhaoJTangHLiuPZhangLet al. Linc00152 promotes tumorigenesis by regulating DNMTs in triple-negative breast cancer. Biomed Pharmacother (2018) 97:1275–81. doi: 10.1016/j.biopha.2017.11.055
275
ZhengZ-KPangCYangYDuanQZhangJLiuW-C. Serum long noncoding RNA urothelial carcinoma-associated 1: A novel biomarker for diagnosis and prognosis of hepatocellular carcinoma. J Int Med Res (2018) 46(1):348–56. doi: 10.1177/0300060517726441
276
ZhangJWeiHYangH. Long noncoding RNA SNHG15, a potential prognostic biomarker for hepatocellular carcinoma. Eur Rev Med Pharmacol Sci (2016) 20(9):1720–4.
277
TuZ-QLiR-JMeiJ-ZLiX-H. Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol (2014) 7(7):4303.
278
FuCXuXLuWNieLYinTWuD. Increased expression of long non-coding RNA CCAT2 predicts poorer prognosis in patients with hepatocellular carcinoma. Medicine (2019) 98(42):e17412. doi: 10.1097/MD.0000000000017412
279
WangYJingWMaWLiangCChaiHTuJ. Down-regulation of long non-coding RNA GAS5-AS1 and its prognostic and diagnostic significance in hepatocellular carcinoma. Cancer Biomarkers (2018) 22(2):227–36. doi: 10.3233/CBM-170781
280
MaWWangHJingWZhouFChangLHongZet al. Downregulation of long non-coding RNAs JPX and XIST is associated with the prognosis of hepatocellular carcinoma. Clinics Res Hepatol Gastroenterol (2017) 41(2):163–70. doi: 10.1016/j.clinre.2016.09.002
281
LiS-YWangHMaiH-FLiG-FChenS-JLiG-Set al. Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway. Cancer Gene Ther (2019) 26(11):374–87. doi: 10.1038/s41417-018-0066-6
282
ZengZDongJLiYDongZLiuZHuangJet al. The expression level and clinical significance of lncRNA X91348 in hepatocellular carcinoma. Artif Cells Nanomed Biotechnol (2019) 47(1):3067–71. doi: 10.1080/21691401.2019.1640228
283
ChenQTianGWangC. Expression of lncRNA TCONS_00027978 in hepatocellular carcinoma and its influence on prognosis and survival. Eur Rev Med Pharmacol Sci (2017) 21(24):5655–60. doi: 10.26355/eurrev_201712_14009
284
GuJ-XZhangXMiaoR-CXiangX-HFuY-NZhangJ-Yet al. Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma. World J Gastroenterol (2019) 25(2):220. doi: 10.3748/wjg.v25.i2.220
285
RefaiNSLoukaMLHalimHYMontasserI. Long non-coding RNAs (CASC2 and TUG1) in hepatocellular carcinoma: Clinical significance. J Gene Med (2019) 21(9):e3112. doi: 10.1002/jgm.3112
286
ZhaoQ-JZhangJXuLLiuF-F. Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma. World J Gastroenterol (2018) 24(30):3426. doi: 10.3748/wjg.v24.i30.3426
287
ShakerOGAbdelwahedMYAhmedNAHassanEAAhmedTIAbousarieMAet al. Evaluation of serum long noncoding RNA NEAT and MiR-129-5p in hepatocellular carcinoma. IUBMB Life (2019) 71(10):1571–8. doi: 10.1002/iub.2096
288
GuoSChenWLuoYRenFZhongTRongMet al. Clinical implication of long non-coding RNA NEAT1 expression in hepatocellular carcinoma patients. Int J Clin Exp Pathol (2015) 8(5):5395.
289
TangJJiangRDengLZhangXWangKSunB. Circulation long non-coding RNAs act as biomarkers for predicting tumorigenesis and metastasis in hepatocellular carcinoma. Oncotarget (2015) 6(6):4505. doi: 10.18632/oncotarget.2934
290
MaYLuoTDongDWuXWangY. Characterization of long non-coding RNAs to reveal potential prognostic biomarkers in hepatocellular carcinoma. Gene (2018) 663:148–56. doi: 10.1016/j.gene.2018.04.053
291
XuHChenYDongXWangX. Serum exosomal long noncoding RNAs ENSG00000258332. 1 and LINC00635 for the diagnosis and prognosis of hepatocellular carcinoma. Cancer Epidemiol Prev Biomarkers (2018) 27(6):710–6. doi: 10.1158/1055-9965.EPI-17-0770
292
ChaoYZhouD. lncRNA-D16366 Is a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma. Med Sci Monitor: Int Med J Exp Clin Res (2019) 25:6581. doi: 10.12659/MSM.915100
293
HabiebAMatboliMEl-TayebHEl-AsmarF. Potential role of lncRNA-TSIX, miR-548-a-3p, and SOGA1 mRNA in the diagnosis of hepatocellular carcinoma. Mol Biol Rep (2019) 46(4):4581–90. doi: 10.1007/s11033-019-04810-x
294
ZengY-LGuoZ-YSuH-ZZhongF-DJiangK-QYuanG-D. Diagnostic and prognostic value of lncRNA cancer susceptibility candidate 9 in hepatocellular carcinoma. World J Gastroenterol (2019) 25(48):6902. doi: 10.3748/wjg.v25.i48.6902
295
LuoPLiangCZhangXLiuXWangYWuMet al. Identification of long non-coding RNA ZFAS1 as a novel biomarker for diagnosis of HCC. Biosci Rep (2018) 38(4):BSR20171359. doi: 10.1042/BSR20171359
296
WangCRenTWangKZhangSLiuSChenHet al. Identification of long non-coding RNA p34822 as a potential plasma biomarker for the diagnosis of hepatocellular carcinoma. Sci China Life Sci (2017) 60(9):1047. doi: 10.1007/s11427-017-9054-y
297
XieZZhouFYangYLiLLeiYLinXet al. Lnc-PCDH9-13: 1 is a hypersensitive and specific biomarker for early hepatocellular carcinoma. EBioMedicine (2018) 33:57–67. doi: 10.1016/j.ebiom.2018.06.026
298
LiuX-FThinKZMingX-L-LiS-LuoP-ZhuMet al. Small nucleolar RNA host gene 18 acts as a tumor suppressor and a diagnostic indicator in hepatocellular carcinoma. Technol Cancer Res Treat (2018) 17:1533033818794494. doi: 10.1177/1533033818794494
299
GaoSXuXWangYZhangWWangX. Diagnostic utility of plasma lncRNA small nucleolar RNA host gene 1 in patients with hepatocellular carcinoma. Mol Med Rep (2018) 18(3):3305–13. doi: 10.3892/mmr.2018.9336
300
ZhuSHuangXZhangKTanWLinZHeQet al. Low expression of long noncoding RNA CTC-297N7. 9 predicts poor prognosis in patients with hepatocellular carcinoma. Cancer Med (2019) 8(18):7679–92. doi: 10.1002/cam4.2618
301
MotawiTMEl-MaraghySASabryDMehanaNA. The expression of long non coding RNA genes is associated with expression with polymorphisms of HULC rs7763881 and MALAT1 rs619586 in hepatocellular carcinoma and HBV Egyptian patients. J Cell Biochem (2019) 120(9):14645–56. doi: 10.1002/jcb.28726
302
TaoRHuSWangSZhouXZhangQWangCet al. Association between indel polymorphism in the promoter region of lncRNA GAS5 and the risk of hepatocellular carcinoma. Carcinogenesis (2015) 36(10):1136–43. doi: 10.1093/carcin/bgv099
303
WanJHuangMZhaoHWangCZhaoXJiangXet al. A novel tetranucleotide repeat polymorphism within KCNQ1OT1 confers risk for hepatocellular carcinoma. DNA Cell Biol (2013) 32(11):628–34. doi: 10.1089/dna.2013.2118
304
O’BrienAZhouTTanCAlpiniGGlaserS. Role of Non-Coding RNAs in the Progression of Liver Cancer: Evidence from Experimental Models. Cancers (Basel) (2019) 11(11):1652. doi: 10.3390/cancers11111652
305
ZhangHXingZManiSKKBancelBDurantelDZoulimFet al. RNA helicase DEAD box protein 5 regulates Polycomb repressive complex 2/Hox transcript antisense intergenic RNA function in hepatitis B virus infection and hepatocarcinogenesis. Hepatology (2016) 64(4):1033–48. doi: 10.1002/hep.28698
306
ChenZZHuangLWuYHZhaiWJZhuPPGaoYF. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression. Nat Commun (2016) 7:12598. doi: 10.1038/ncomms12598
307
ZhangH-TZengL-FHeQ-YTaoWAZhaZ-GHuC-D. The E3 ubiquitin ligase CHIP mediates ubiquitination and proteasomal degradation of PRMT5. Biochim Biophys Acta (BBA)-Molecular Cell Res (2016) 1863(2):335–46. doi: 10.1016/j.bbamcr.2015.12.001
308
DingC-HYinCChenS-JWenL-ZDingKLeiS-Jet al. The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1. Mol Cancer (2018) 17(1):1–14. doi: 10.1186/s12943-018-0813-1
309
KoppFMendellJT. Functional classification and experimental dissection of long noncoding RNAs. Cell (2018) 172(3):393–407. doi: 10.1016/j.cell.2018.01.011
310
ArunGDiermeierSDSpectorDL. Therapeutic targeting of long non-coding RNAs in cancer. Trends Mol Med (2018) 24(3):257–77. doi: 10.1016/j.molmed.2018.01.001
Summary
Keywords
lncRNA, biomarker, hepatocellular carcinoma, expression, polymorphism
Citation
Ghafouri-Fard S, Gholipour M, Hussen BM and Taheri M (2021) The Impact of Long Non-Coding RNAs in the Pathogenesis of Hepatocellular Carcinoma. Front. Oncol. 11:649107. doi: 10.3389/fonc.2021.649107
Received
03 January 2021
Accepted
22 March 2021
Published
21 April 2021
Volume
11 - 2021
Edited by
Xing-Xing He, Huazhong University of Science and Technology, China
Reviewed by
Ying Chang, Wuhan University, China; Min Wang, Huazhong University of Science and Technology, China
Updates
Copyright
© 2021 Ghafouri-Fard, Gholipour, Hussen and Taheri.
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.
*Correspondence: Mohammad Taheri, mohammad_823@yahoo.com
This article was submitted to Gastrointestinal Cancers, a section of the journal Frontiers in Oncology
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