Skip to main content
SpringerLink
Log in

MicroRNAs and hepatitis viruses

  • Review
  • Published:
Frontiers of Medicine in China Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are a class of small RNA molecules. They play a pivotal role in diverse domains such as infection, tumorigenesis, and immune reaction. As key regulators of most genes’ expression, they react at posttranscriptional level. It is increasingly clear that miRNAs are necessary for physiological and pathological processes. In the past few years, investigators gradually brought the concept of miRNA into studies of viral infection, including hepatitis viruses. The hepatitis B and C viruses are common causes of liver disease worldwide. It is very difficult to cure chronic hepatitis due to drug resistance during antivirus therapy. Elucidating the mechanisms of virus-host interactions in hepatitis B and C is very important in diagnosis, prognosis, and therapy. This article reviews the current knowledge of viral hepatitis (types B and C) at the level of miRNA and tries to outline areas of potential studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lee Y, Kim M, Han J, Yeom K H, Lee S, Baek S H, Kim V N. MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 2004, 23(20): 4051–4060

    Article  PubMed  CAS  Google Scholar 

  2. Lund E, Güttinger S, Calado A, Dahlberg J E, Kutay U. Nuclear export of microRNA precursors. Science, 2004, 303(5654): 95–98

    Article  PubMed  CAS  Google Scholar 

  3. Gottwein E, Cullen B R. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe, 2008, 3(6): 375–387

    Article  PubMed  CAS  Google Scholar 

  4. Ghosh Z, Mallick B, Chakrabarti J. Cellular versus viral micro-RNAs in host-virus interaction. Nucleic Acids Res, 2009, 37(4): 1035–1048

    Article  PubMed  CAS  Google Scholar 

  5. Yu Z, Jian Z, Shen S H, Purisima E, Wang E. Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos. Nucleic Acids Res, 2007, 35(1): 152–164

    Article  PubMed  CAS  Google Scholar 

  6. Sun R, Fu X, Li Y, Xie Y, Mao Y. Global gene expression analysis reveals reduced abundance of putative microRNA targets in human prostate tumours. BMC Genomics, 2009, 10: 93

    Article  PubMed  Google Scholar 

  7. Schmittgen T D, Lee E J, Jiang J, Sarkar A, Yang L, Elton T S, Chen C. Real-time PCR quantification of precursor and mature micro-RNA. Methods, 2008, 44(1): 31–38

    Article  PubMed  CAS  Google Scholar 

  8. Rajewsky N. MicroRNA target predictions in animals. Nat Genet, 2006, 38(Suppl): S8–13

    Article  PubMed  CAS  Google Scholar 

  9. Papadopoulos G L, Reczko M, Simossis V A, Sethupathy P, Hatzigeorgiou A G. The database of experimentally supported targets: a functional update of TarBase. Nucleic Acids Res, 2009, 37 (Database issue): D155–158

    Article  PubMed  CAS  Google Scholar 

  10. Canales R D, Luo Y, Willey J C, Austermiller B, Barbacioru C C, Boysen C, Hunkapiller K, Jensen RV, Knight C R, Lee K Y, Ma Y, Maqsodi B, Papallo A, Peters E H, Poulter K, Ruppel P L, Samaha R R, Shi L, Yang W, Zhang L, Goodsaid F M. Evaluation of DNA microarray results with quantitative gene expression platforms. Nat Biotechnol, 2006, 24: 1115–1122

    Article  PubMed  CAS  Google Scholar 

  11. Arikawa E, Sun Y, Wang J, Zhou Q, Ning B, Dial SL, Guo L, Yang J. Cross-platform comparison of SYBR Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study. BMC Genomics, 2008, 9: 328

    Article  PubMed  Google Scholar 

  12. Cullen B R. Viruses and microRNAs. Nat Genet, 2006, 38(Suppl): S25–30

    Article  PubMed  CAS  Google Scholar 

  13. Jin W B, Wu F L, Kong D, Guo A G. HBV-encoded microRNA candidate and its target. Comput Biol Chem, 2007, 31(2): 124–126

    Article  PubMed  CAS  Google Scholar 

  14. Li Z, Zhang S, Huang C, Zhang W, Hu Y, Wei B. MicroRNAome of splenic macrophages in hypersplenism due to portal hypertension in hepatitis B virus-related cirrhosis. Exp Biol Med (Maywood), 2008, 233(11): 1454–1461

    Article  CAS  Google Scholar 

  15. Gao Y F, Yu L, Wei W, Li J B, Luo Q L, Shen J L. Inhibition of hepatitis B virus gene expression and replication by artificial microRNA. World J Gastroenterol, 2008, 14(29): 4684–4689

    Article  PubMed  CAS  Google Scholar 

  16. Esau C, Davis S, Murray S F, Yu X X, Pandey S K, Pear M, Watts L, Booten S L, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP. MiR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab, 2006, 3(2): 87–98

    Article  PubMed  CAS  Google Scholar 

  17. Shan Y, Zheng J, Lambrecht R W, Bonkovsky H L. Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology, 2007, 133(4): 1166–1174

    Article  PubMed  CAS  Google Scholar 

  18. Lebanony D, Benjamin H, Gilad S, Ezagouri M, Dov A, Ashkenazi K, Gefen N, Izraeli S, Rechavi G, Pass H, Nonaka D, Li J, Spector Y, Rosenfeld N, Chajut A, Cohen D, Aharonov R, Mansukhani M. Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. J Clin Oncol, 2009, 27(12): 2030–2037

    Article  PubMed  CAS  Google Scholar 

  19. Merritt W M, Lin Y G, Han L Y, Kamat A A, Spannuth W A, Schmandt R, Urbauer D, Pennacchio L A, Cheng J F, Nick A M, Deavers MT, Mourad-Zeidan A, Wang H, Mueller P, Lenburg ME, Gray J W, Mok S, Birrer M J, Lopez-Berestein G, Coleman R L, Bar-Eli M, Sood A K. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med, 2008, 359(25): 2641–2650

    Article  PubMed  CAS  Google Scholar 

  20. Slack F J, Weidhaas J B. MicroRNA in cancer prognosis. N Engl J Med, 2008, 359(25): 2720–2722

    Article  PubMed  CAS  Google Scholar 

  21. O’Donnell K A, Wentzel E A, Zeller K I, Dang C V, Mendell J T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature, 2005, 435(7043): 839–843

    Article  PubMed  Google Scholar 

  22. Liu Y, Zhao J J, Wang C M, Li M Y, Han P, Wang L, Cheng Y Q, Zoulim F, Ma X, Xu D P. Altered expression profiles of microRNAs in a stable hepatitis B virus-expressing cell line. Chin Med J (Engl), 2009, 122(1): 10–14

    CAS  Google Scholar 

  23. Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S, Zucman-Rossi J. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology, 2008, 47(6): 1955–1963

    Article  PubMed  CAS  Google Scholar 

  24. Wong QW, Lung RW, Law P T, Lai P B, Chan K Y, To K F, Wong N. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology, 2008, 135(1): 257–269

    Article  PubMed  CAS  Google Scholar 

  25. 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(4): 1098–1112

    Article  PubMed  CAS  Google Scholar 

  26. Ito Y, Matsuura N, Sakon M, Miyoshi E, Noda K, Takeda T, Umeshita K, Nagano H, Nakamori S, Dono K, Tsujimoto M, Nakahara M, Nakao K, Taniguchi N, Monden M. Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 independently predicts the recurrence. Hepatology, 1999, 30(1): 90–99

    Article  PubMed  CAS  Google Scholar 

  27. Jing Z, Nan K J, Hu M L. Cell proliferation, apoptosis and the related regulators p27, p53 expression in hepatocellular carcinoma. World J Gastroenterol, 2005, 11(13): 1910–1916

    PubMed  CAS  Google Scholar 

  28. Varnholt H, Drebber U, Schulze F, Wedemeyer I, Schirmacher P, Dienes H P, Odenthal M. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology, 2008, 47(4): 1223–1232

    Article  PubMed  CAS  Google Scholar 

  29. Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu C G, Calin G A, Giovannini C, Ferrazzi E, Grazi G L, Croce C M, Bolondi L, Negrini M. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res, 2007, 67(13): 6092–6099

    Article  PubMed  CAS  Google Scholar 

  30. Shehata M A, Nosseir H R, Nagy H M, Farouk G. Cyclin dependent kinase inhibitor p27(kip1) expression and subcellular localization in relation to cell proliferation in hepatocellualr carcinoma. Egypt J Immunol, 2006, 13(1): 115–130

    PubMed  Google Scholar 

  31. Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin G A, Grazi G L, Giovannini C, Croce C M, Bolondi L, Negrini M. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene, 2008, 27(43): 5651–5661

    Article  PubMed  CAS  Google Scholar 

  32. Connolly E, Melegari M, Landgraf P, Tchaikovskaya T, Tennant B C, Slagle B L, Rogler L E, Zavolan M, Tuschl T, Rogler C E. Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. Am J Pathol, 2008, 173(3): 856–864

    Article  PubMed  CAS  Google Scholar 

  33. Su H, Yang J R, Xu T, Huang J, Xu L, Yuan Y, Zhuang S M. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res, 2009, 69(3): 1135–1142

    Article  PubMed  CAS  Google Scholar 

  34. Fleischer B, Schulze-Bergkamen H, Schuchmann M, Weber A, Biesterfeld S, Müller M, Krammer P H, Galle P R. Mcl-1 is an antiapoptotic factor for human hepatocellular carcinoma. Int J Oncol. 2006, 28(1): 25–32

    PubMed  CAS  Google Scholar 

  35. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob S T, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology, 2007, 133 (2): 647–658

    Article  PubMed  CAS  Google Scholar 

  36. Jopling C L, Yi M, Lancaster A M, Lemon S M, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science, 2005, 309(5740): 1577–1581

    Article  PubMed  CAS  Google Scholar 

  37. Chang J, Guo J T, Jiang D, Guo H, Taylor J M, Block T M. Liverspecific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells. J Virol, 2008, 82(16): 8215–8223

    Article  PubMed  CAS  Google Scholar 

  38. Henke J I, Goergen D, Zheng J, Song Y, Schüttler C G, Fehr C, Jünemann C, Niepmann M. MicroRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J, 2008, 27(24): 3300–3310

    Article  PubMed  CAS  Google Scholar 

  39. Murakami Y, Aly H H, Tajima A, Inoue I, Shimotohno K. Regulation of the hepatitis C virus genome replication by miR-199a. J Hepatol, 2009, 50(3): 453–460

    Article  PubMed  CAS  Google Scholar 

  40. Gao Y F, Yu L, Wei W, Li J B, Luo Q L, Shen J L. Inhibition of hepatitis B virus gene expression and replication by artificial microRNA. World J Gastroenterol, 2008, 14(29): 4684–4689

    Article  PubMed  CAS  Google Scholar 

  41. Ely A, Naidoo T, Mufamadi S, Crowther C, Arbuthnot P. Expressed anti-HBV primary microRNA shuttles inhibit viral replication efficiently in vitro and in vivo. Mol Ther, 2008, 16(6): 1105–1112

    Article  PubMed  CAS  Google Scholar 

  42. Pedersen I M, Cheng G, Wieland S, Volinia S, Croce C M, Chisari F V, David M. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature, 2007, 449(7164): 919–922

    Article  PubMed  CAS  Google Scholar 

  43. Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim M H, Filipowicz W. Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med, 2009, 15(1): 31–33

    Article  PubMed  CAS  Google Scholar 

  44. Georgantas R W 3rd, Hildreth R, Morisot S, Alder J, Liu C G, Heimfeld S, Calin G A, Croce C M, Civin C I. CD34 + hematopoietic stem-progenitor cell microRNA expression and function: A circuit diagram of differentiation control. Proc Natl Acad Sci U S A, 2007, 104(8): 2750–2755

    Article  PubMed  CAS  Google Scholar 

  45. Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R, Volinia S, Bhatt D, Alder H, Marcucci G, Calin G A, Liu C G, Bloomfield C D, Andreeff M, Croce C M. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci U S A, 2006, 103(13): 5078–5083

    Article  PubMed  CAS  Google Scholar 

  46. Rodriguez A, Vigorito E, Clare S, Warren M V, Couttet P, Soond D R, van Dongen S, Grocock R J, Das P P, Miska E A, Vetrie D, Okkenhaug K, Enright A J, Dougan G, Turner M, Bradley A. Requirement of bic/microRNA-155 for normal immune function. Science, 2007, 316(5824): 608–611

    Article  PubMed  CAS  Google Scholar 

  47. O’Connell R M, Taganov K D, Boldin M P, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A, 2007, 104(5): 1604–1609

    Article  PubMed  Google Scholar 

  48. Ceppi M, Pereira P M, Dunand-Sauthier I, Barras E, Reith W, Santos M A, Pierre P. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci U S A, 2009, 106(8): 2735–2740

    Article  PubMed  CAS  Google Scholar 

  49. Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, Huang W, Squires K, Verlinghieri G, Zhang H. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4 + T lymphocytes. Nat Med, 2007, 13(10): 1241–1247

    Article  PubMed  CAS  Google Scholar 

  50. Jiang J, Lee E J, Schmittgen T D. Increased expression of mi microRNA-155 in Epstein-Barr virus transformed lymphoblastoid cell lines. Genes Chromosomes Cancer, 2006, 45(1): 103–106

    Article  PubMed  CAS  Google Scholar 

  51. Yin Q, McBride J, Fewell C, Lacey M, Wang X, Lin Z, Cameron J, Flemington E K. MicroRNA-155 is an Epstein-Barr virus-induced gene that modulates Epstein-Barr virus-regulated gene expression pathways. J Virol, 2008, 82(11): 5295–5306

    Article  PubMed  CAS  Google Scholar 

  52. Cameron J E, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer B C, Flemington E K. Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol, 2008, 82(4): 1946–1958

    Article  PubMed  CAS  Google Scholar 

  53. Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M. Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res, 2008, 36(20): 6608–6619

    Article  PubMed  CAS  Google Scholar 

  54. Stern-Ginossar N, Elefant N, Zimmermann A, Wolf D G, Saleh N, Biton M, Horwitz E, Prokocimer Z, Prichard M, Hahn G, Goldman-Wohl D, Greenfield C, Yagel S, Hengel H, Altuvia Y, Margalit H, Mandelboim O. Host immune system gene targeting by a viral miRNA. Science, 2007, 317(5836): 376–381

    Article  PubMed  CAS  Google Scholar 

  55. Dustin L B, Rice C M. Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol, 2007, 25: 71–99

    Article  PubMed  CAS  Google Scholar 

  56. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol, 2005, 5(3): 215–229

    Article  PubMed  CAS  Google Scholar 

  57. Shiina M, Rehermann B. Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function. Hepatology, 2008, 47 (2): 385–395

    Article  PubMed  CAS  Google Scholar 

  58. Rigopoulou E I, Abbott W G, Williams R, Naoumov N V. Direct evidence for immunomodulatory properties of ribavirin on T-cell reactivity to hepatitis C virus. Antiviral Res, 2007, 75(1): 36–42

    Article  PubMed  CAS  Google Scholar 

  59. Lu G F, Tang F A, Zheng P Y, Yang P C, Qi Y M. Entecavir upregulates dendritic cell function in patients with chronic hepatitis B. World J Gastroenterol, 2008, 14(10): 1617–1621

    Article  PubMed  CAS  Google Scholar 

  60. Zheng P Y, Zhang D Y, Lu G F, Yang P C, Qi Y M, Wang B S. Effects of lamivudine on the function of dendritic cells derived from patients with chronic hepatitis B virus infection. World J Gastroenterol, 2007, 13(34): 4641–4645

    PubMed  CAS  Google Scholar 

  61. Saito T, Gale M Jr. Regulation of innate immunity against hepatitis C virus infection. Hepatol Res, 2008, 38(2): 115–122

    PubMed  CAS  Google Scholar 

  62. Ye L, Wang X, Wang S, Wang Y, Song L, Hou W, Zhou L, Li H, Ho W. CD56 + T cells inhibit hepatitis C virus replication in human hepatocytes. Hepatology, 2009, 49(3): 753–762

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

    Gang Li & Xiaojia Xiong

Authors
  1. Gang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaojia Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gang Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, G., Xiong, X. MicroRNAs and hepatitis viruses. Front. Med. China 3, 265–270 (2009). https://doi.org/10.1007/s11684-009-0055-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-009-0055-0

Keywords

Search

Navigation