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microRNAs and Hepatitis B

  • Yutaka Naito
  • Yasuhito Tanaka
  • Takahiro Ochiya
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 888)

Abstract

The hepatitis B virus (HBV) infection is the leading cause of persistent liver diseases, cirrhosis, and hepatocellular carcinoma (HCC). However, the precise mechanism underlying the development of HBV-related diseases is not fully understood. In addition, the therapeutic strategies for the diseases are less than optimum. microRNAs (miRNAs) are small noncoding RNAs that have been described as a “fine-tuner” in various cellular events. The dysregulation of miRNAs play a role in the development of the cancer as well as viral interference. Recent articles have demonstrated that several miRNAs are deregulated by HBV infection and contribute to viral replication and pathogenesis. Thus, it suggests that the precise mechanism between miRNA and HBV biology will be leading to the development of the novel diagnosis and therapy. This chapter aims to provide the basic principals of miRNAs in development of the HBV-related diseases. We also discuss about the possibility of miRNAs on the clinical application for diagnosis and therapy of HBV-related diseases.

Keywords

microRNA Hepatitis B virus Hepatocellular carcinoma 

Notes

Acknowledgement

This study was supported by grants from the Ministry of Health, Labour, and Welfare of Japan.

References

  1. 1.
    Zhao X, Wu Y, Duan J, Ma Y, Shen Z, Wei L, Cui X, Zhang J, Xie Y, Liu J. Quantitative proteomic analysis of exosome protein content changes induced by hepatitis B virus in Huh-7 cells using SILAC labeling and LC-MS/MS. J Proteome Res. 2014;13:5391–402.CrossRefPubMedGoogle Scholar
  2. 2.
    Arzumanyan A, Reis HM, Feitelson MA. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 2013;13:123–35.CrossRefPubMedGoogle Scholar
  3. 3.
    Protzer U, Maini MK, Knolle PA. Living in the liver: hepatic infections. Nat Rev Immunol. 2012;12:201–13.CrossRefPubMedGoogle Scholar
  4. 4.
    Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–44.CrossRefPubMedGoogle Scholar
  5. 5.
    Godon O, Fontaine H, Kahi S, Meritet J, Scott-Algara D, Pol S, Michel M, Bourgine M. Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues. Mol Ther. 2014;22:675–84.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350:1118–29.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang X, Hou J, Lu M. Regulation of hepatitis B virus replication by epigenetic mechanisms and microRNAs. Front Genet. 2013;4:202.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology. 2007;46:1759–68.CrossRefPubMedGoogle Scholar
  9. 9.
    Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife. 2012;1, e00049.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bock CT, Schranz P, Schroder CH, Zentgraf H. Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell. Virus Genes. 1994;8:215–29.CrossRefPubMedGoogle Scholar
  11. 11.
    Newbold JE, Xin H, Tencza M, Sherman G, Dean J, Bowden S, Locarnini S. The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes. J Virol. 1995;69:3350–7.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.PubMedGoogle Scholar
  13. 13.
    Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Comput Biol Chem. 2007;31:124–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhang X, Zhang E, Ma Z, Pei R, Jiang M, Schlaak JF, Roggendorf M, Lu M. Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1. Hepatology. 2011;53:1476–85.CrossRefPubMedGoogle Scholar
  15. 15.
    Reese V, Ondracek C, Rushing C, Li L, Oropeza CE, McLachlan A. Multiple nuclear receptors may regulate hepatitis B virus biosynthesis during development. Int J Biochem Cell Biol. 2011;43:230–7.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Levrero M, Pollicino T, Petersen J, Belloni L, Raimondo G, Dandri M. Control of cccDNA function in hepatitis B virus infection. J Hepatol. 2009;51:581–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Guo H, Liu H, Mitchelson K, Rao H, Luo M, Xie L, Sun Y, Zhang L, Lu Y, Liu R, Ren A, Liu S, Zhou S, Zhu J, Zhou Y, Huang A, Wei L, Guo Y, Cheng J. MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B. Hepatology. 2011;54:808–19.CrossRefPubMedGoogle Scholar
  18. 18.
    Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25:2537–45.CrossRefPubMedGoogle Scholar
  19. 19.
    Hou J, Lin L, Zhou W, Wang Z, Ding G, Dong Q, Qin L, Wu X, Zheng Y, Yang Y, Tian W, Zhang Q, Wang C, Zhang Q, Zhuang SM, Zheng L, Liang A, Tao W, Cao X. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 2011;19:232–43.CrossRefPubMedGoogle Scholar
  20. 20.
    Jin J, Tang S, Xia L, Du R, Xie H, Song J, Fan R, Bi Q, Chen Z, Yang G, Liu J, Shi Y, Fan D. MicroRNA-501 promotes HBV replication by targeting HBXIP. Biochem Biophys Res Commun. 2013;430:1228–33.CrossRefPubMedGoogle Scholar
  21. 21.
    Melegari M, Scaglioni PP, Wands JR. Cloning and characterization of a novel hepatitis B virus x binding protein that inhibits viral replication. J Virol. 1998;72:1737–43.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Dai X, Zhang W, Zhang H, Sun S, Yu H, Guo Y, Kou Z, Zhao G, Du L, Jiang S, Zhang J, Li J, Zhou Y. Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1alpha. Nucleic Acids Res. 2014;42:6578–90.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chung GE, Yoon JH, Myung SJ, Lee JH, Lee SH, Lee SM, Kim SJ, Hwang SY, Lee HS, Kim CY. High expression of microRNA-15b predicts a low risk of tumor recurrence following curative resection of hepatocellular carcinoma. Oncol Rep. 2010;23:113–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, Poon RT, Gao C, Luk JM. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2:e000825.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Girard M, Jacquemin E, Munnich A, Lyonnet S, Henrion-Caude A. miR-122, a paradigm for the role of microRNAs in the liver. J Hepatol. 2008;48:648–56.CrossRefPubMedGoogle Scholar
  26. 26.
    Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 2005;309:1577–81.CrossRefPubMedGoogle Scholar
  27. 27.
    Chen Y, Shen A, Rider PJ, Yu Y, Wu K, Mu Y, Hao Q, Liu Y, Gong H, Zhu Y, Liu F, Wu J. A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication. FASEB J. 2011;25:4511–21.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wang S, Qiu L, Yan X, Jin W, Wang Y, Chen L, Wu E, Ye X, Gao GF, Wang F, Chen Y, Duan Z, Meng S. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity. Hepatology. 2012;55:730–41.CrossRefPubMedGoogle Scholar
  29. 29.
    Potenza N, Papa U, Mosca N, Zerbini F, Nobile V, Russo A. Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen. Nucleic Acids Res. 2011;39:5157–63.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Mosca N, Castiello F, Coppola N, Trotta MC, Sagnelli C, Pisaturo M, Sagnelli E, Russo A, Potenza N. Functional interplay between hepatitis B virus X protein and human miR-125a in HBV infection. Biochem Biophys Res Commun. 2014;449:141–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Kohno T, Tsuge M, Murakami E, Hiraga N, Abe H, Miki D, Imamura M, Ochi H, Hayes CN, Chayama K. Human microRNA hsa-miR-1231 suppresses hepatitis B virus replication by targeting core mRNA. J Viral Hepat. 2014;21:e89–97.CrossRefPubMedGoogle Scholar
  32. 32.
    Huang J, Wang Y, Guo Y, Sun S. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 2010;52:60–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9:839–45.CrossRefPubMedGoogle Scholar
  34. 34.
    O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007;104:1604–9.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007;179:5082–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Berasain C, Castillo J, Perugorria MJ, Latasa MU, Prieto J, Avila MA. Inflammation and liver cancer: new molecular links. Ann N Y Acad Sci. 2009;1155:206–21.CrossRefPubMedGoogle Scholar
  37. 37.
    Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, Schmittgen TD, Croce C, Ghoshal K, Jacob ST. Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice. Hepatology. 2009;50:1152–61.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Su C, Hou Z, Zhang C, Tian Z, Zhang J. Ectopic expression of microRNA-155 enhances innate antiviral immunity against HBV infection in human hepatoma cells. Virol J. 2011;8:354.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Liu Y, Zhao JJ, Wang CM, Li MY, Han P, Wang L, Cheng YQ, Zoulim F, Ma X, Xu DP. Altered expression profiles of microRNAs in a stable hepatitis B virus-expressing cell line. Chin Med J (Engl). 2009;122:10–4.CrossRefGoogle Scholar
  40. 40.
    Li LM, Hu ZB, Zhou ZX, Chen X, Liu FY, Zhang JF, Shen HB, Zhang CY, Zen K. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 2010;70:9798–807.CrossRefPubMedGoogle Scholar
  41. 41.
    Kogure T, Lin WL, Yan IK, Braconi C, Patel T. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology. 2011;54:1237–48.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, Wang JF, Zhang Z, Lu S, Huang X, Wang Z, Qiu S, Wang X, Yang G, Sun H, Tang Z, Wu Y, Zhu H, Fan J. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol. 2011;29:4781–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Waidmann O, Bihrer V, Pleli T, Farnik H, Berger A, Zeuzem S, Kronenberger B, Piiper A. Serum microRNA-122 levels in different groups of patients with chronic hepatitis B virus infection. J Viral Hepat. 2012;19:e58–65.CrossRefPubMedGoogle Scholar
  44. 44.
    Arataki K, Hayes CN, Akamatsu S, Akiyama R, Abe H, Tsuge M, Miki D, Ochi H, Hiraga N, Imamura M, Takahashi S, Aikata H, Kawaoka T, Kawakami H, Ohishi W, Chayama K. Circulating microRNA-22 correlates with microRNA-122 and represents viral replication and liver injury in patients with chronic hepatitis B. J Med Virol. 2013;85:789–98.CrossRefPubMedGoogle Scholar
  45. 45.
    Xing TJ, Xu HT, Yu WQ, Wang B, Zhang J. MiRNA-548ah, a potential molecule associated with transition from immune tolerance to immune activation of chronic hepatitis B. Int J Mol Sci. 2014;15:14411–26.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Li L, Guo Z, Wang J, Mao Y, Gao Q. Serum miR-18a: a potential marker for hepatitis B virus-related hepatocellular carcinoma screening. Dig Dis Sci. 2012;57:2910–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Ura S, Honda M, Yamashita T, Ueda T, Takatori H, Nishino R, Sunakozaka H, Sakai Y, Horimoto K, Kaneko S. Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology. 2009;49:1098–112.CrossRefPubMedGoogle Scholar
  48. 48.
    Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137:1005–17.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Qiu L, Fan H, Jin W, Zhao B, Wang Y, Ju Y, Chen L, Chen Y, Duan Z, Meng S. miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV. Biochem Biophys Res Commun. 2010;398:771–7.Google Scholar
  50. 50.
    Wang YQ, Ren YF, Song YJ, Xue YF, Zhang XJ, Cao ST, Deng ZJ, Wu J, Chen L, Li G, Shi KQ, Chen YP, Ren H, Huang AL, Tang KF. MicroRNA-581 promotes hepatitis B virus surface antigen expression by targeting Dicer and EDEM1. Carcinogenesis. 2014;35:2127–33.Google Scholar
  51. 51.
    Wang Y, Jiang L, Ji X, Yang B, Zhang Y, Fu XD. Hepatitis B viral RNA directly mediates down-regulation of the tumor suppressor microRNA miR-15a/miR-16-1 in hepatocytes. J Biol Chem. 2013;288:18484–93.Google Scholar
  52. 52.
    Jung YJ, Kim JW, Park SJ, Min BY, Jang ES, Kim NY, Jeong SH, Shin CM, Lee SH, Park YS, Hwang JH, Kim N, Lee DH. c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells. J Med Virol. 2013;85:969–78.Google Scholar
  53. 53.
    Hu W, Wang X, Ding X, Li Y, Zhang X, Xie P, Yang J, Wang S. MicroRNA-141 represses HBV replication by targeting PPARA. PLoS One. 2012;7:e34165.Google Scholar
  54. 54.
    Wang S, Zhang X, Ju Y, Zhao B, Yan X, Hu J, Shi L, Yang L, Ma Z, Chen L, Liu Y, Duan Z, Chen X, Meng S. MicroRNA-146a feedback suppresses T cell immune function by targeting Stat1 in patients with chronic hepatitisB. J Immunol. 2013;191:293–301.Google Scholar
  55. 55.
    Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H. Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antiviral Res. 2010;88:169–75.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Yutaka Naito
    • 1
  • Yasuhito Tanaka
    • 2
  • Takahiro Ochiya
    • 1
  1. 1.Division of Molecular and Cellular MedicineNational Cancer Center Research InstituteChuo-kuJapan
  2. 2.Department of Virology and Liver UnitNagoya City University Graduate School of Medical SciencesNagoyaJapan

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