- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
TAO Chuanmin,
Email: taocm@scu.edu.cn
Long non-coding RNA (lncRNA) is a type of nucleic acid sequence that exceeds 200 nucleotides in length and cannot encode any complete protein. In recent years, its important regulatory role in various pathophysiological processes has been gradually clarified, however, few studies have reported its role in carcinogenic virus infection. This article summarizes the currently known lncRNAs abnormally expressed in hepatitis B virus-induced hepatocellular carcinoma, and focuses on the mechanisms of lncRNAs regulating the occurrence and development of hepatitis B virus-related hepatocellular carcinoma such as controlling virus replication and host immunity, cell cycle and proliferation, invasion and metastasis, autophagy and apoptosis of liver cancer cells, hoping to provide a theoretical basis for the molecular targeted therapy of hepatocellular carcinoma.
Citation： FENG Shu, TAO Chuanmin. Research progress of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma. West China Medical Journal, 2020, 35(8): 983-990. doi: 10.7507/1002-0179.202007031 Copy
| 1. | Liang TJ. Hepatitis B: the virus and disease. Hepatology, 2009, 49(5): S13-S21. |
| 2. | Islami F, Chen W, Yu XQ, <italic>et al</italic>. Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013. Ann Oncol, 2017, 28(10): 2567-2574. |
| 3. | de Martel C, Georges D, Bray F, <italic>et al</italic>. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health, 2020, 8(2): e180-e190. |
| 4. | Sartorius K, Makarova J, Sartorius B, <italic>et al</italic>. The regulatory role of microRNA in hepatitis-B virus-associated hepatocellular carcinoma (HBV-HCC) pathogenesis. Cells, 2019, 8(12): 1504. |
| 5. | Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol, 2011, 21(6): 354-361. |
| 6. | Cougot D, Neuveut C, Buendia MA. HBV induced carcinogenesis. J Clin Virol, 2005, 34: S75-S78. |
| 7. | Lemoine M, Thursz MR. Battlefield against hepatitis B infection and HCC in Africa. J Hepatol, 2017, 66(3): 645-654. |
| 8. | Mak D, de Villiers CB, Chasela C, <italic>et al</italic>. Analysis of risk factors associated with hepatocellular carcinoma in black South Africans: 2000–2012. PloS one, 2018, 13(5): e0196057. |
| 9. | Levrero M, Zucman Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol, 2016, 64(1): S84-S101. |
| 10. | Xu C, Zhou WC, Wang YM, <italic>et al</italic>. Hepatitis B virus-induced hepatocellular carcinoma. Cancer Lett, 2014, 345(2, SI): 216-222. |
| 11. | Heikenwalder M, Protzer U. LINE(1)s of evidence in HBV-driven liver cancer. Cell Host Microbe, 2014, 15(3): 249-250. |
| 12. | Lau CC, Sun T, Ching AK, <italic>et al</italic>. Viral-human chimeric transcript predisposes risk to liver cancer development and progression. Cancer Cell, 2014, 25(3): 335-349. |
| 13. | Wang S, Qiu L, Yan X, <italic>et al</italic>. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G1-modulated P53 activity. Hepatology, 2012, 55(3): 730-741. |
| 14. | Hao J, Jin W, Li X, <italic>et al</italic>. Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α. J Virol, 2013, 87(1): 137-147. |
| 15. | Qiu LP, Wang T, Xu XQ, <italic>et al</italic>. Long non-coding RNAs in hepatitis B Virus-related hepatocellular carcinoma: regulation, functions, and underlying mechanisms. Int J Mol Sci, 2017, 18(12): 2505. |
| 16. | Yilmaz Susluer S, Kayabasi C, Ozmen Yelken B, <italic>et al</italic>. Analysis of long non-coding RNA (lncRNA) expression in hepatitis B patients. Bosn J Basic Med Sci, 2018, 18(2): 150-161. |
| 17. | Feng J, Yang G, Liu YX, <italic>et al</italic>. LncRNA PCNAP1 modulates hepatitis B virus replication and enhances tumor growth of liver cancer. Theranostics, 2019, 9(18): 5227-5245. |
| 18. | Yang G, Feng JY, Liu YX, <italic>et al</italic>. HAT1 signaling confers to assembly and epigenetic regulation of HBV cccDNA minichromosome. Theranostics, 2019, 9(24): 7345-7358. |
| 19. | Salerno D, Chiodo L, Alfano V, et al. Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription. Gut. (2020-02-09)[2020-07-02]. http://dx.doi.org/10.1136/gutjnl-2019-319637. |
| 20. | Zhuang L, Tian JH, Zhang XZ, <italic>et al</italic>. Lnc-DC regulates cellular turnover and the HBV-induced immune response by TLR9/STAT3 signaling in dendritic cells. Cell Mol Biol Lett, 2018, 23(1): 43. |
| 21. | Li H, Zhao XN, Li CH, <italic>et al</italic>. Integrated analysis of lncRNA-associated ceRNA network reveals potential biomarkers for the prognosis of hepatitis B virus-related hepatocellular carcinoma. Cancer Manag Res, 2019, 11: 877-897. |
| 22. | Zhong R, Tian JB, Fu M, <italic>et al</italic>. LINC01149 variant modulates MICA expression that facilitates hepatitis B virus spontaneous recovery but increases hepatocellular carcinoma risk. Oncogene, 2020, 39(9): 1944-1956. |
| 23. | Nishitsuji H, Ujino S, Yoshio S, <italic>et al</italic>. Long noncoding RNA 32 contributes to antiviral responses by controlling interferon-stimulated gene expression. Proc Natl Acad Sci USA, 2016, 113(37): 10388-10393. |
| 24. | Wen J, Liu Y, Liu J, <italic>et al</italic>. Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development. Mol Carcinog, 2015, 54(11): 1275-1282. |
| 25. | Du YM, Kong GY, You XN, <italic>et al</italic>. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18. J Biol Chem, 2012, 287(31): 26302-26311. |
| 26. | Zhang H, Diab A, Fan HT, <italic>et al</italic>. PLK1 and HOTAIR accelerate proteasomal degradation of SUZ12 and ZNF198 during hepatitis B virus-induced liver carcinogenesis. Cancer Res, 2015, 75(11): 2363-2374. |
| 27. | Hu JJ, Song W, Zhang SD, <italic>et al</italic>. HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling. Sci Rep, 2016, 6(1): 23521. |
| 28. | Hou Z, Xu XW, Fu XY, <italic>et al</italic>. HBx-related long non-coding RNA MALAT1 promotes cell metastasis via up-regulating LTBP3 in hepatocellular carcinoma. Am J Cancer Res, 2017, 7(4): 845-856. |
| 29. | Huang JL, Ren TY, Cao SW, <italic>et al</italic>. HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget, 2015, 6(32): 33791-33804. |
| 30. | Hu Z, Huang P, Yan YC, <italic>et al</italic>. Hepatitis B virus X protein related lncRNA WEE2-AS1 promotes hepatocellular carcinoma proliferation and invasion. Biochem Biophys Res Commun, 2019, 508(1): 79-86. |
| 31. | Lv J, Fan HX, Zhao XP, <italic>et al</italic>. Long non-coding RNA Unigene56159 promotes epithelial mesenchymal transition by acting as a ceRNA of miR-140-5p in hepatocellular carcinoma cells. Cancer Lett, 2016, 382(2): 166-175. |
| 32. | Yuan SX, Yang F, Yang Y, <italic>et al</italic>. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology, 2012, 56(6): 2231-2241. |
| 33. | Yang F, Zhang L, Huo XS, <italic>et al</italic>. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology, 2011, 54(5): 1679-1689. |
| 34. | Lu J, Xie F, Geng L, <italic>et al</italic>. Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV. Tumour Biol, 2015, 36(5): 3231-3236. |
| 35. | Ruan L, Huang L, Zhao L, <italic>et al</italic>. The interaction of lncRNA-HEIH and lncRNA-HULC with HBXIP in hepatitis B patients. Gastroenterol Res Pract, 2018, 2018: 9187316. |
| 36. | Wang J, Liu X, Wu H, <italic>et al</italic>. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res, 2010, 38(16): 5366-5383. |
| 37. | Li D, Liu XE, Zhou J, <italic>et al</italic>. 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): 1612-1627. |
| 38. | Fu WM, Zhu X, Wang WM, <italic>et al</italic>. Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling. J Hepatol, 2015, 63(4): 886-895. |
| 39. | Tu W, Yang YH, Song YL, <italic>et al</italic>. Hepatitis B virus x protein accelerated the proliferation of hepatocellular carcinoma cell through lncRNA SNHG20/PTEN pathway. J Biochem, 2019, 165(5): 423-431. |
| 40. | Liu Y, Feng JY, Sun MM, <italic>et al</italic>. Long non-coding RNA HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related hepatocellular carcinoma. Cancer Lett, 2019, 454: 158-170. |
| 41. | Wang F, Ying HQ, He BS, <italic>et al</italic>. Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget, 2015, 6(10): 7899-7917. |
| 42. | Huang JF, Wang YE, Liu F, <italic>et al</italic>. EVI1 promotes cell proliferation in HBx-induced hepatocarcinogenesis as a critical transcription factor regulating lncRNAs. Oncotarget, 2016, 7(16): 21887-21899. |
| 43. | Liu N, Liu Q, Yang X, <italic>et al</italic>. Hepatitis B Virus-Upregulated LNC-HUR1 promotes cell proliferation and tumorigenesis by blocking p53 activity. Hepatology, 2018, 68(6): 2130-2144. |
| 44. | Chen T, Pei J, Wang J, <italic>et al</italic>. HBx-related long non-coding RNA 01152 promotes cell proliferation and survival by IL-23 in hepatocellular carcinoma. Biomed Pharmacother, 2019, 115: 108877. |
| 45. | Liu Q, Liu N, Shangguan Q, <italic>et al</italic>. LncRNA SAMD12-AS1 promotes cell proliferation and inhibits apoptosis by interacting with NPM1. Sci Rep, 2019, 9(1): 11593. |
| 46. | Huang JF, Guo YJ, Zhao CX, <italic>et al</italic>. Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology, 2013, 57(5): 1882-1892. |
| 47. | Moyo B, Nicholson SA, Arbuthnot PB. The role of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma. Virus Res, 2016, 212: 103-113. |
| 48. | Yu S, Li N, Huang ZB, <italic>et al</italic>. A novel lncRNA, TCONS_00006195, represses hepatocellular carcinoma progression by inhibiting enzymatic activity of ENO1. Cell Death Dis, 2018, 9(12): 1184. |
| 49. | Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest, 2009, 119(6): 1420-1428. |
| 50. | Yang Z, Zhou L, Wu LM, <italic>et al</italic>. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol, 2011, 18(5): 1243-1250. |
| 51. | Xiao JN, Yan TH, Yu RM, <italic>et al</italic>. 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): 981-990. |
| 52. | Li SP, Xu HX, Yu Y, <italic>et al</italic>. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway. Oncotarget, 2016, 7(27): 42431-42446. |
| 53. | Zhang Y, Li J, Wang S, <italic>et al</italic>. HBx-associated long non-coding RNA activated by TGF-β promotes cell invasion and migration by inducing autophagy in primary liver cancer. Int J Oncol, 2020, 56(1): 337-347. |
| 54. | Liang HW, Wang N, Wang YB, <italic>et al</italic>. Hepatitis B virus-human chimeric transcript HBx-LINE1 promotes hepatic injury via sequestering cellular microRNA-122. J Hepatol, 2016, 64(2): 278-291. |
| 55. | Deng X, Zhao XF, Liang XQ, <italic>et al</italic>. Linc00152 promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. Biomed Pharmacother, 2017, 90: 100-108. |
| 56. | Jin Y, Wu D, Yang WW, <italic>et al</italic>. Hepatitis B virus x protein induces epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating long non-coding RNA. Virol J, 2017, 14(1): 238. |
| 57. | Fan H, Lv P, Mu T, <italic>et al</italic>. LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells. Cancer Lett, 2018, 429: 89-99. |
| 58. | Chen Z, Yu W, Zhou Q, <italic>et al</italic>. A novel lncRNA IHS promotes tumor proliferation and metastasis in HCC by regulating the ERK- and AKT/GSK-3β-signaling pathways. Mol Ther Nucleic Acids, 2019, 16: 707-720. |
| 59. | Ding C, Cheng S, Yang Z, <italic>et al</italic>. 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): 4060-4076. |
| 60. | Geng YJ, Xie SL, Li Q, <italic>et al</italic>. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res, 2011, 39(6): 2119-2128. |
| 61. | Guo J, Hao C, Wang C, <italic>et al</italic>. Long noncoding RNA PVT1 modulates hepatocellular carcinoma cell proliferation and apoptosis by recruiting EZH2. Cancer Cell Int, 2018, 18(1): 98. |
| 62. | Jiang B, Yang B, Wang Q, <italic>et al</italic>. lncRNA PVT1 promotes hepatitis B virus-positive liver cancer progression by disturbing histone methylation on the c-Myc promoter. Oncol Rep, 2020, 43(2): 718-726. |
| 63. | Yang F, Huo XS, Yuan SX, <italic>et al</italic>. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell, 2013, 49(6): 1083-1096. |
| 64. | Zhang L, Yang F, Yuan JH, <italic>et al</italic>. Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma. Carcinogenesis, 2013, 34(3): 577-586. |
| 65. | Li L, Han T, Liu K, <italic>et al</italic>. LncRNA H19 promotes the development of hepatitis B related hepatocellular carcinoma through regulating microRNA-22 via EMT pathway. Eur Rev Med Pharmacol Sci, 2019, 23(12): 5392-5401. |
| 66. | Deng Y, Wei Z, Huang MJ, <italic>et al</italic>. Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p. J Cell Mol Med, 2020, 24(2): 1848-1865. |
| 67. | Anand SK, Sharma A, Singh N, <italic>et al</italic>. Entrenching role of cell cycle checkpoints and autophagy for maintenance of genomic integrity. DNA Repair (Amst), 2020, 86: 102748. |
| 68. | Xia P, Liu Y, Chen JR, <italic>et al</italic>. Cell cycle proteins as key regulators of postmitotic cell death. Yale J Biol Med, 2019, 92(4): 641-650. |
| 69. | Sir D, Tian Y, Chen WL, <italic>et al</italic>. The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci USA, 2010, 107(9): 4383-4388. |
| 70. | Wu SY, Lan SH, Liu HS. Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol, 2016, 22(1): 176-187. |
| 71. | Yang L, Zhang X, Li H, <italic>et al</italic>. The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma. Mol Biosyst, 2016, 12(8): 2605-2612. |
- 1. Liang TJ. Hepatitis B: the virus and disease. Hepatology, 2009, 49(5): S13-S21.
- 2. Islami F, Chen W, Yu XQ, <italic>et al</italic>. Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013. Ann Oncol, 2017, 28(10): 2567-2574.
- 3. de Martel C, Georges D, Bray F, <italic>et al</italic>. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health, 2020, 8(2): e180-e190.
- 4. Sartorius K, Makarova J, Sartorius B, <italic>et al</italic>. The regulatory role of microRNA in hepatitis-B virus-associated hepatocellular carcinoma (HBV-HCC) pathogenesis. Cells, 2019, 8(12): 1504.
- 5. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol, 2011, 21(6): 354-361.
- 6. Cougot D, Neuveut C, Buendia MA. HBV induced carcinogenesis. J Clin Virol, 2005, 34: S75-S78.
- 7. Lemoine M, Thursz MR. Battlefield against hepatitis B infection and HCC in Africa. J Hepatol, 2017, 66(3): 645-654.
- 8. Mak D, de Villiers CB, Chasela C, <italic>et al</italic>. Analysis of risk factors associated with hepatocellular carcinoma in black South Africans: 2000–2012. PloS one, 2018, 13(5): e0196057.
- 9. Levrero M, Zucman Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol, 2016, 64(1): S84-S101.
- 10. Xu C, Zhou WC, Wang YM, <italic>et al</italic>. Hepatitis B virus-induced hepatocellular carcinoma. Cancer Lett, 2014, 345(2, SI): 216-222.
- 11. Heikenwalder M, Protzer U. LINE(1)s of evidence in HBV-driven liver cancer. Cell Host Microbe, 2014, 15(3): 249-250.
- 12. Lau CC, Sun T, Ching AK, <italic>et al</italic>. Viral-human chimeric transcript predisposes risk to liver cancer development and progression. Cancer Cell, 2014, 25(3): 335-349.
- 13. Wang S, Qiu L, Yan X, <italic>et al</italic>. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G1-modulated P53 activity. Hepatology, 2012, 55(3): 730-741.
- 14. Hao J, Jin W, Li X, <italic>et al</italic>. Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α. J Virol, 2013, 87(1): 137-147.
- 15. Qiu LP, Wang T, Xu XQ, <italic>et al</italic>. Long non-coding RNAs in hepatitis B Virus-related hepatocellular carcinoma: regulation, functions, and underlying mechanisms. Int J Mol Sci, 2017, 18(12): 2505.
- 16. Yilmaz Susluer S, Kayabasi C, Ozmen Yelken B, <italic>et al</italic>. Analysis of long non-coding RNA (lncRNA) expression in hepatitis B patients. Bosn J Basic Med Sci, 2018, 18(2): 150-161.
- 17. Feng J, Yang G, Liu YX, <italic>et al</italic>. LncRNA PCNAP1 modulates hepatitis B virus replication and enhances tumor growth of liver cancer. Theranostics, 2019, 9(18): 5227-5245.
- 18. Yang G, Feng JY, Liu YX, <italic>et al</italic>. HAT1 signaling confers to assembly and epigenetic regulation of HBV cccDNA minichromosome. Theranostics, 2019, 9(24): 7345-7358.
- 19. Salerno D, Chiodo L, Alfano V, et al. Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription. Gut. (2020-02-09)[2020-07-02]. http://dx.doi.org/10.1136/gutjnl-2019-319637.
- 20. Zhuang L, Tian JH, Zhang XZ, <italic>et al</italic>. Lnc-DC regulates cellular turnover and the HBV-induced immune response by TLR9/STAT3 signaling in dendritic cells. Cell Mol Biol Lett, 2018, 23(1): 43.
- 21. Li H, Zhao XN, Li CH, <italic>et al</italic>. Integrated analysis of lncRNA-associated ceRNA network reveals potential biomarkers for the prognosis of hepatitis B virus-related hepatocellular carcinoma. Cancer Manag Res, 2019, 11: 877-897.
- 22. Zhong R, Tian JB, Fu M, <italic>et al</italic>. LINC01149 variant modulates MICA expression that facilitates hepatitis B virus spontaneous recovery but increases hepatocellular carcinoma risk. Oncogene, 2020, 39(9): 1944-1956.
- 23. Nishitsuji H, Ujino S, Yoshio S, <italic>et al</italic>. Long noncoding RNA 32 contributes to antiviral responses by controlling interferon-stimulated gene expression. Proc Natl Acad Sci USA, 2016, 113(37): 10388-10393.
- 24. Wen J, Liu Y, Liu J, <italic>et al</italic>. Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development. Mol Carcinog, 2015, 54(11): 1275-1282.
- 25. Du YM, Kong GY, You XN, <italic>et al</italic>. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18. J Biol Chem, 2012, 287(31): 26302-26311.
- 26. Zhang H, Diab A, Fan HT, <italic>et al</italic>. PLK1 and HOTAIR accelerate proteasomal degradation of SUZ12 and ZNF198 during hepatitis B virus-induced liver carcinogenesis. Cancer Res, 2015, 75(11): 2363-2374.
- 27. Hu JJ, Song W, Zhang SD, <italic>et al</italic>. HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling. Sci Rep, 2016, 6(1): 23521.
- 28. Hou Z, Xu XW, Fu XY, <italic>et al</italic>. HBx-related long non-coding RNA MALAT1 promotes cell metastasis via up-regulating LTBP3 in hepatocellular carcinoma. Am J Cancer Res, 2017, 7(4): 845-856.
- 29. Huang JL, Ren TY, Cao SW, <italic>et al</italic>. HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget, 2015, 6(32): 33791-33804.
- 30. Hu Z, Huang P, Yan YC, <italic>et al</italic>. Hepatitis B virus X protein related lncRNA WEE2-AS1 promotes hepatocellular carcinoma proliferation and invasion. Biochem Biophys Res Commun, 2019, 508(1): 79-86.
- 31. Lv J, Fan HX, Zhao XP, <italic>et al</italic>. Long non-coding RNA Unigene56159 promotes epithelial mesenchymal transition by acting as a ceRNA of miR-140-5p in hepatocellular carcinoma cells. Cancer Lett, 2016, 382(2): 166-175.
- 32. Yuan SX, Yang F, Yang Y, <italic>et al</italic>. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology, 2012, 56(6): 2231-2241.
- 33. Yang F, Zhang L, Huo XS, <italic>et al</italic>. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology, 2011, 54(5): 1679-1689.
- 34. Lu J, Xie F, Geng L, <italic>et al</italic>. Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV. Tumour Biol, 2015, 36(5): 3231-3236.
- 35. Ruan L, Huang L, Zhao L, <italic>et al</italic>. The interaction of lncRNA-HEIH and lncRNA-HULC with HBXIP in hepatitis B patients. Gastroenterol Res Pract, 2018, 2018: 9187316.
- 36. Wang J, Liu X, Wu H, <italic>et al</italic>. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res, 2010, 38(16): 5366-5383.
- 37. Li D, Liu XE, Zhou J, <italic>et al</italic>. 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): 1612-1627.
- 38. Fu WM, Zhu X, Wang WM, <italic>et al</italic>. Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling. J Hepatol, 2015, 63(4): 886-895.
- 39. Tu W, Yang YH, Song YL, <italic>et al</italic>. Hepatitis B virus x protein accelerated the proliferation of hepatocellular carcinoma cell through lncRNA SNHG20/PTEN pathway. J Biochem, 2019, 165(5): 423-431.
- 40. Liu Y, Feng JY, Sun MM, <italic>et al</italic>. Long non-coding RNA HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related hepatocellular carcinoma. Cancer Lett, 2019, 454: 158-170.
- 41. Wang F, Ying HQ, He BS, <italic>et al</italic>. Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget, 2015, 6(10): 7899-7917.
- 42. Huang JF, Wang YE, Liu F, <italic>et al</italic>. EVI1 promotes cell proliferation in HBx-induced hepatocarcinogenesis as a critical transcription factor regulating lncRNAs. Oncotarget, 2016, 7(16): 21887-21899.
- 43. Liu N, Liu Q, Yang X, <italic>et al</italic>. Hepatitis B Virus-Upregulated LNC-HUR1 promotes cell proliferation and tumorigenesis by blocking p53 activity. Hepatology, 2018, 68(6): 2130-2144.
- 44. Chen T, Pei J, Wang J, <italic>et al</italic>. HBx-related long non-coding RNA 01152 promotes cell proliferation and survival by IL-23 in hepatocellular carcinoma. Biomed Pharmacother, 2019, 115: 108877.
- 45. Liu Q, Liu N, Shangguan Q, <italic>et al</italic>. LncRNA SAMD12-AS1 promotes cell proliferation and inhibits apoptosis by interacting with NPM1. Sci Rep, 2019, 9(1): 11593.
- 46. Huang JF, Guo YJ, Zhao CX, <italic>et al</italic>. Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology, 2013, 57(5): 1882-1892.
- 47. Moyo B, Nicholson SA, Arbuthnot PB. The role of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma. Virus Res, 2016, 212: 103-113.
- 48. Yu S, Li N, Huang ZB, <italic>et al</italic>. A novel lncRNA, TCONS_00006195, represses hepatocellular carcinoma progression by inhibiting enzymatic activity of ENO1. Cell Death Dis, 2018, 9(12): 1184.
- 49. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest, 2009, 119(6): 1420-1428.
- 50. Yang Z, Zhou L, Wu LM, <italic>et al</italic>. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol, 2011, 18(5): 1243-1250.
- 51. Xiao JN, Yan TH, Yu RM, <italic>et al</italic>. 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): 981-990.
- 52. Li SP, Xu HX, Yu Y, <italic>et al</italic>. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway. Oncotarget, 2016, 7(27): 42431-42446.
- 53. Zhang Y, Li J, Wang S, <italic>et al</italic>. HBx-associated long non-coding RNA activated by TGF-β promotes cell invasion and migration by inducing autophagy in primary liver cancer. Int J Oncol, 2020, 56(1): 337-347.
- 54. Liang HW, Wang N, Wang YB, <italic>et al</italic>. Hepatitis B virus-human chimeric transcript HBx-LINE1 promotes hepatic injury via sequestering cellular microRNA-122. J Hepatol, 2016, 64(2): 278-291.
- 55. Deng X, Zhao XF, Liang XQ, <italic>et al</italic>. Linc00152 promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. Biomed Pharmacother, 2017, 90: 100-108.
- 56. Jin Y, Wu D, Yang WW, <italic>et al</italic>. Hepatitis B virus x protein induces epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating long non-coding RNA. Virol J, 2017, 14(1): 238.
- 57. Fan H, Lv P, Mu T, <italic>et al</italic>. LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells. Cancer Lett, 2018, 429: 89-99.
- 58. Chen Z, Yu W, Zhou Q, <italic>et al</italic>. A novel lncRNA IHS promotes tumor proliferation and metastasis in HCC by regulating the ERK- and AKT/GSK-3β-signaling pathways. Mol Ther Nucleic Acids, 2019, 16: 707-720.
- 59. Ding C, Cheng S, Yang Z, <italic>et al</italic>. 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): 4060-4076.
- 60. Geng YJ, Xie SL, Li Q, <italic>et al</italic>. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res, 2011, 39(6): 2119-2128.
- 61. Guo J, Hao C, Wang C, <italic>et al</italic>. Long noncoding RNA PVT1 modulates hepatocellular carcinoma cell proliferation and apoptosis by recruiting EZH2. Cancer Cell Int, 2018, 18(1): 98.
- 62. Jiang B, Yang B, Wang Q, <italic>et al</italic>. lncRNA PVT1 promotes hepatitis B virus-positive liver cancer progression by disturbing histone methylation on the c-Myc promoter. Oncol Rep, 2020, 43(2): 718-726.
- 63. Yang F, Huo XS, Yuan SX, <italic>et al</italic>. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell, 2013, 49(6): 1083-1096.
- 64. Zhang L, Yang F, Yuan JH, <italic>et al</italic>. Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma. Carcinogenesis, 2013, 34(3): 577-586.
- 65. Li L, Han T, Liu K, <italic>et al</italic>. LncRNA H19 promotes the development of hepatitis B related hepatocellular carcinoma through regulating microRNA-22 via EMT pathway. Eur Rev Med Pharmacol Sci, 2019, 23(12): 5392-5401.
- 66. Deng Y, Wei Z, Huang MJ, <italic>et al</italic>. Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p. J Cell Mol Med, 2020, 24(2): 1848-1865.
- 67. Anand SK, Sharma A, Singh N, <italic>et al</italic>. Entrenching role of cell cycle checkpoints and autophagy for maintenance of genomic integrity. DNA Repair (Amst), 2020, 86: 102748.
- 68. Xia P, Liu Y, Chen JR, <italic>et al</italic>. Cell cycle proteins as key regulators of postmitotic cell death. Yale J Biol Med, 2019, 92(4): 641-650.
- 69. Sir D, Tian Y, Chen WL, <italic>et al</italic>. The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci USA, 2010, 107(9): 4383-4388.
- 70. Wu SY, Lan SH, Liu HS. Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol, 2016, 22(1): 176-187.
- 71. Yang L, Zhang X, Li H, <italic>et al</italic>. The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma. Mol Biosyst, 2016, 12(8): 2605-2612.