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microRNAs and Hepatitis B

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Book cover microRNA: Medical Evidence

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  2. Arzumanyan A, Reis HM, Feitelson MA. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 2013;13:123–35.

    Article  CAS  PubMed  Google Scholar 

  3. Protzer U, Maini MK, Knolle PA. Living in the liver: hepatic infections. Nat Rev Immunol. 2012;12:201–13.

    Article  CAS  PubMed  Google Scholar 

  4. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–44.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350:1118–29.

    Article  CAS  PubMed  Google Scholar 

  7. Zhang X, Hou J, Lu M. Regulation of hepatitis B virus replication by epigenetic mechanisms and microRNAs. Front Genet. 2013;4:202.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.

    CAS  PubMed  Google Scholar 

  13. Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Comput Biol Chem. 2007;31:124–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. 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. 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. 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. 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. 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. 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 

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Acknowledgement

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

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Authors and Affiliations

  1. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yutaka Naito & Takahiro Ochiya

  2. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Yasuhito Tanaka

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  1. Yutaka Naito
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  2. Yasuhito Tanaka
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  3. Takahiro Ochiya
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Correspondence to Takahiro Ochiya .

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Editors and Affiliations

  1. Columbia University Medical Center, New York, New York, USA

    Gaetano Santulli

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Naito, Y., Tanaka, Y., Ochiya, T. (2015). microRNAs and Hepatitis B. In: Santulli, G. (eds) microRNA: Medical Evidence. Advances in Experimental Medicine and Biology, vol 888. Springer, Cham. https://doi.org/10.1007/978-3-319-22671-2_19

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