微 RNA 在乙型肝炎相关疾病中作用研究进展_West China Medical Journal

Authors：

曹丹 , 袁满 , 余乐 ,  王丽春

四川大学华西医院感染性疾病中心/生物治疗国家重点实验室感染性疾病研究室（成都 610041）;

Corresponding author：

王丽春, Email: mindywang0218@163.com

Keywords：

微 RNA; 乙型肝炎病毒; 肝纤维化; 肝衰竭; 肝癌

DOI：

10.7507/1002-0179.201702178

Video：

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Abstract Full text Figures/Tables Video References Cited by

乙型肝炎病毒（hepatitis B virus，HBV）感染是造成肝纤维化、肝衰竭和肝癌的主要原因。微 RNA（microRNA，miRNA）在 HBV 慢性感染状态下出现异常表达。部分表达异常的 miRNA 可以通过活化肝星状细胞或产生胶原蛋白来促进肝纤维化过程；也可以通过诱导肝细胞短期内大量坏死或凋亡来加速肝衰竭进展；亦可以通过上调癌基因或下调抑癌基因表达促进癌症的发生与发展。该文初步探讨了 miRNA 在肝纤维化、肝衰竭、肝癌中的作用。

Citation： 曹丹, 袁满, 余乐, 王丽春. 微 RNA 在乙型肝炎相关疾病中作用研究进展. West China Medical Journal, 2017, 32(11): 1810-1813. doi: 10.7507/1002-0179.201702178 Copy

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2.	Riazalhosseini B, Mohamed R, Apalasamy YD, et al. Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B. Rev Soc Bras Med Trop, 2017, 50(2): 161-166.
3.	Deng WY, Lu MJ. The role of microRNAs in hepatocyte metabolism and hepatitis B virus replication. Virol Sin, 2016, 31(6): 472-479.
4.	Hayes CN, Chayama K. MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci, 2016, 17(3): 280.
5.	Chen R, Wu JC, Liu T, et al. MicroRNA profile analysis in the liver fibrotic tissues of chronic hepatitis B patients. J Dig Dis, 2017, 18(2): 115-124.
6.	Shah N, Nelson JE, Kowdley KV. MicroRNAs in liver disease: bench to bedside. J Clin Exp Hepatol, 2013, 3(3): 231-242.
7.	Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab, 2006, 3(2): 87-98.
8.	Qiu L, Fan H, Jin W, et al. miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV. Biochem Biophys Res Commun, 2010, 398(4): 771-777.
9.	Wang S, Qiu L, Yan X, et al. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity. Hepatology, 2012, 55(3): 730-741.
10.	Huang JY, Chou SF, Lee JW, et al. MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ. RNA, 2015, 21(3): 385-400.
11.	Zhang X, Liu H, Xie Z, et al. Epigenetically regulated miR-449a enhances hepatitis B virus replication by targeting cAMP-responsive element binding protein 5 and modulating hepatocytes phenotype. Sci Rep, 2016, 6: 25389.
12.	Fan H, Lv P, Lv J, et al. miR-370 suppresses HBV gene expression and replication by targeting nuclear factor IA. J Med Virol, 2017, 89(5): 834-844.
13.	Huang JY, Chen HL, Shih C. MicroRNA miR-204 and miR-1236 inhibit hepatitis B virus replication via two different mechanisms. Sci Rep, 2016, 6: 34740.
14.	Lakner AM, Steuerwald NM, Walling TL, et al. Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis. Hepatology, 2012, 56(1): 300-310.
15.	Huang CF, Sun CC, Zhao F, et al. miR-33a levels in hepatic and serum after chronic HBV-induced fibrosis. J Gastroenterol, 2015, 50(4): 480-490.
16.	Tu X, Zhang H, Zhang J, et al. MicroRNA-101 suppresses liver fibrosis by targeting the TGFβ signalling pathway. J Pathol, 2014, 234(1): 46-59.
17.	Hyun J, Wang S, Kim J, et al. MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression. Nat Commun, 2016, 7: 10993.
18.	Sun J, Zhang H, Li L, et al. MicroRNA-9 limits hepatic fibrosis by suppressing the activation and proliferation of hepatic stellate cells by directly targeting MRP1/ABCC1. Oncol Rep, 2017, 37(3): 1698-1706.
19.	Kwiecinski M, Elfimova N, Noetel A, et al. Expression of platelet-derived growth factor-C and insulin-like growth factorⅠ in hepatic stellate cells is inhibited by miR-29. Lab Invest, 2012, 92(7): 978-987.
20.	中华医学会感染病学分会肝衰竭与人工肝学组. 肝衰竭诊治指南(2012 年版). 实用器官移植电子杂志, 2013, 1(4): 193-202.
21.	Guicciardi ME, Malhi H, Mott JL, et al. Apoptosis and necrosis in the liver. Compr Physiol, 2013, 3(2): 977-1010.
22.	An F, Gong B, Wang H, et al. miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure. Apoptosis, 2012, 17(7): 702-716.
23.	Yu DS, An FM, Gong BD, et al. The regulatory role of microRNA-1187 in TNF-α-mediated hepatocyte apoptosis in acute liver failure. Int J Mol Med, 2012, 29(4): 663-668.
24.	Yang F, Lou G, Zhou X, et al. MicroRNA-223 acts as an important regulator to Kupffer cells activation at the early stage of Con A-induced acute liver failure via AIM2 signaling pathway. Cell Physiol Biochem, 2014, 34(6): 2137-2152.
25.	Li ZY, Xi Y, Zhu WN, et al. Positive regulation of hepatic miR-122 expression by HNF4α. J Hepatol, 2011, 55(3): 602-611.
26.	John K, Hadem J, Krech T, et al. MicroRNAs play a role in spontaneous recovery from acute liver failure. Hepatology, 2014, 60(4): 1346-1355.
27.	Ramamoorthy A, Li L, Gaedigk A, et al. In silico and in vitro identification of microRNAs that regulate hepatic nuclear factor 4α expression. Drug Metab Dispos, 2012, 40(4): 726-733.
28.	Jiang H, He X, Li J, et al. Association of a single-nucleotide polymorphism within the miR-146a gene with susceptibility for acute-on-chronic hepatitis B liver failure. Immunogenetics, 2013, 65(4): 257-263.
29.	Zheng QF, Zhang JY, Wu JS, et al. Upregulation of miRNA-130a represents good prognosis in patients with HBV-related acute-on-chronic liver failure: a prospective study. Medicine(Baltimore), 2016, 95(6): e2639.
30.	Zou C, Chen J, Chen K, et al. Functional analysis of miR-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis. Exp Cell Res, 2015, 331(2): 352-361.
31.	Zou C, Li Y, Cao Y, et al. Up-regulated MicroRNA-181a induces carcinogenesis in Hepatitis B virus-related hepatocellular carcinoma by targeting E2F5. BMC Cancer, 2014, 14: 97.
32.	Kong XX, Lv YR, Shao LP, et al. HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells. J Transl Med, 2016, 14(1): 189.
33.	Yin D, Wang Y, Sai W, et al. HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12. Oncol Rep, 2016, 36(4): 2305-2312.
34.	Gao F, Sun X, Wang L, et al. Downregulation of MicroRNA-145 caused by hepatitis B virus X protein promotes expression of CUL5 and contributes to pathogenesis of hepatitis B virus-associated hepatocellular carcinoma. Cell Physiol Biochem, 2015, 37(4): 1547-1559.
35.	Deng M, Hou J, Hu J, et al. Hepatitis B virus mRNAs functionally sequester let-7a and enhance hepatocellular carcinoma. Cancer Lett, 2016, 383(1): 62-72.
36.	Chen JS, Li HS, Huang JQ, et al. MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma. Cancer Lett, 2016, 375(1): 73-83.
37.	Naito Y, Tanaka Y, Ochiya T. microRNAs and Hepatitis B. Adv Exp Med Biol, 2015, 888: 389-399.
38.	Zhang Q, Xu M, QU Y, et al. Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection. Mol Med Rep, 2015, 12(4): 5647-5654.
39.	Lamontagne J, Steel LF, Bouchard MJ. Hepatitis B virus and microRNAs: complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases. World J Gastroenterol, 2015, 21(24): 7375-7399.

1. Newman MA, Hammond SM. Emerging paradigms of regulated microRNA processing. Genes Dev, 2010, 24(11): 1086-1092.
2. Riazalhosseini B, Mohamed R, Apalasamy YD, et al. Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B. Rev Soc Bras Med Trop, 2017, 50(2): 161-166.
3. Deng WY, Lu MJ. The role of microRNAs in hepatocyte metabolism and hepatitis B virus replication. Virol Sin, 2016, 31(6): 472-479.
4. Hayes CN, Chayama K. MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci, 2016, 17(3): 280.
5. Chen R, Wu JC, Liu T, et al. MicroRNA profile analysis in the liver fibrotic tissues of chronic hepatitis B patients. J Dig Dis, 2017, 18(2): 115-124.
6. Shah N, Nelson JE, Kowdley KV. MicroRNAs in liver disease: bench to bedside. J Clin Exp Hepatol, 2013, 3(3): 231-242.
7. Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab, 2006, 3(2): 87-98.
8. Qiu L, Fan H, Jin W, et al. miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV. Biochem Biophys Res Commun, 2010, 398(4): 771-777.
9. Wang S, Qiu L, Yan X, et al. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity. Hepatology, 2012, 55(3): 730-741.
10. Huang JY, Chou SF, Lee JW, et al. MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ. RNA, 2015, 21(3): 385-400.
11. Zhang X, Liu H, Xie Z, et al. Epigenetically regulated miR-449a enhances hepatitis B virus replication by targeting cAMP-responsive element binding protein 5 and modulating hepatocytes phenotype. Sci Rep, 2016, 6: 25389.
12. Fan H, Lv P, Lv J, et al. miR-370 suppresses HBV gene expression and replication by targeting nuclear factor IA. J Med Virol, 2017, 89(5): 834-844.
13. Huang JY, Chen HL, Shih C. MicroRNA miR-204 and miR-1236 inhibit hepatitis B virus replication via two different mechanisms. Sci Rep, 2016, 6: 34740.
14. Lakner AM, Steuerwald NM, Walling TL, et al. Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis. Hepatology, 2012, 56(1): 300-310.
15. Huang CF, Sun CC, Zhao F, et al. miR-33a levels in hepatic and serum after chronic HBV-induced fibrosis. J Gastroenterol, 2015, 50(4): 480-490.
16. Tu X, Zhang H, Zhang J, et al. MicroRNA-101 suppresses liver fibrosis by targeting the TGFβ signalling pathway. J Pathol, 2014, 234(1): 46-59.
17. Hyun J, Wang S, Kim J, et al. MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression. Nat Commun, 2016, 7: 10993.
18. Sun J, Zhang H, Li L, et al. MicroRNA-9 limits hepatic fibrosis by suppressing the activation and proliferation of hepatic stellate cells by directly targeting MRP1/ABCC1. Oncol Rep, 2017, 37(3): 1698-1706.
19. Kwiecinski M, Elfimova N, Noetel A, et al. Expression of platelet-derived growth factor-C and insulin-like growth factorⅠ in hepatic stellate cells is inhibited by miR-29. Lab Invest, 2012, 92(7): 978-987.
20. 中华医学会感染病学分会肝衰竭与人工肝学组. 肝衰竭诊治指南(2012 年版). 实用器官移植电子杂志, 2013, 1(4): 193-202.
21. Guicciardi ME, Malhi H, Mott JL, et al. Apoptosis and necrosis in the liver. Compr Physiol, 2013, 3(2): 977-1010.
22. An F, Gong B, Wang H, et al. miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure. Apoptosis, 2012, 17(7): 702-716.
23. Yu DS, An FM, Gong BD, et al. The regulatory role of microRNA-1187 in TNF-α-mediated hepatocyte apoptosis in acute liver failure. Int J Mol Med, 2012, 29(4): 663-668.
24. Yang F, Lou G, Zhou X, et al. MicroRNA-223 acts as an important regulator to Kupffer cells activation at the early stage of Con A-induced acute liver failure via AIM2 signaling pathway. Cell Physiol Biochem, 2014, 34(6): 2137-2152.
25. Li ZY, Xi Y, Zhu WN, et al. Positive regulation of hepatic miR-122 expression by HNF4α. J Hepatol, 2011, 55(3): 602-611.
26. John K, Hadem J, Krech T, et al. MicroRNAs play a role in spontaneous recovery from acute liver failure. Hepatology, 2014, 60(4): 1346-1355.
27. Ramamoorthy A, Li L, Gaedigk A, et al. In silico and in vitro identification of microRNAs that regulate hepatic nuclear factor 4α expression. Drug Metab Dispos, 2012, 40(4): 726-733.
28. Jiang H, He X, Li J, et al. Association of a single-nucleotide polymorphism within the miR-146a gene with susceptibility for acute-on-chronic hepatitis B liver failure. Immunogenetics, 2013, 65(4): 257-263.
29. Zheng QF, Zhang JY, Wu JS, et al. Upregulation of miRNA-130a represents good prognosis in patients with HBV-related acute-on-chronic liver failure: a prospective study. Medicine(Baltimore), 2016, 95(6): e2639.
30. Zou C, Chen J, Chen K, et al. Functional analysis of miR-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis. Exp Cell Res, 2015, 331(2): 352-361.
31. Zou C, Li Y, Cao Y, et al. Up-regulated MicroRNA-181a induces carcinogenesis in Hepatitis B virus-related hepatocellular carcinoma by targeting E2F5. BMC Cancer, 2014, 14: 97.
32. Kong XX, Lv YR, Shao LP, et al. HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells. J Transl Med, 2016, 14(1): 189.
33. Yin D, Wang Y, Sai W, et al. HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12. Oncol Rep, 2016, 36(4): 2305-2312.
34. Gao F, Sun X, Wang L, et al. Downregulation of MicroRNA-145 caused by hepatitis B virus X protein promotes expression of CUL5 and contributes to pathogenesis of hepatitis B virus-associated hepatocellular carcinoma. Cell Physiol Biochem, 2015, 37(4): 1547-1559.
35. Deng M, Hou J, Hu J, et al. Hepatitis B virus mRNAs functionally sequester let-7a and enhance hepatocellular carcinoma. Cancer Lett, 2016, 383(1): 62-72.
36. Chen JS, Li HS, Huang JQ, et al. MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma. Cancer Lett, 2016, 375(1): 73-83.
37. Naito Y, Tanaka Y, Ochiya T. microRNAs and Hepatitis B. Adv Exp Med Biol, 2015, 888: 389-399.
38. Zhang Q, Xu M, QU Y, et al. Analysis of the differential expression of circulating microRNAs during the progression of hepatic fibrosis in patients with chronic hepatitis B virus infection. Mol Med Rep, 2015, 12(4): 5647-5654.
39. Lamontagne J, Steel LF, Bouchard MJ. Hepatitis B virus and microRNAs: complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases. World J Gastroenterol, 2015, 21(24): 7375-7399.

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微 RNA 在乙型肝炎相关疾病中作用研究进展

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