Skip to main content
Log in

The role of microRNAs in Hepatitis C Virus replication and related liver diseases

  • Minireview
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). However, only limited therapeutic options and no vaccines are currently available against HCV infection. Recent studies of microRNAs (miRNAs), which are able to regulate HCV replication and its related liver diseases by directly interacting with the HCV genome or indirectly controlling virus-associated host pathways, have broadened our understanding of the HCV life cycle. HCV utilizes host cellular miRNAs and modulates expression of miRNAs in infected hepatocytes for its infection and propagation. Moreover, such miRNAs directly or indirectly alter HCV replication efficiency and induce liver diseases including liver fibrosis, cirrhosis, or HCC. Representatively, miR-122 directly modulates the HCV life cycle by increasing HCV translation and genomic RNA stability. Recently, a phase IIa clinical trial with miravirsen, an LNA form of antimiR-122 oligonucleotides, showed significant reduction in serum HCV levels in patients chronically infected with HCV with no detectible evidence of resistance. In addition to miR-122, other miRNAs involved in the regulation of HCV propagation could be targeted in strategies to modulate HCV replication and pathogenesis. In this review, we summarize the features of miRNAs critical for HCV replication and HCV-mediated liver abnormalities and briefly discuss their potential application as therapeutic reagents for the treatment of HCV infection and its related diseases.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Refrerences

  • Ariumi Y., Kuroki M., Kushima Y., Osugi K., Hijikata M., Maki M., Ikeda M., and Kato N. 2011. Hepatitis C virus hijacks Pbody and stress granule components around lipid droplets. J. Virol. 85, 6882–6892.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bandyopadhyay S., Friedman R.C., Marquez R.T., Keck K., Kong B., Icardi M.S., Brown K.E., Burge C.B., Schmidt W.N., Wang Y., and et al. 2011. Hepatitis C virus infection and hepatic stellate cell activation downregulate miR-29: miR-29 overexpression reduces hepatitis C viral abundance in culture. J. Infect. Dis. 203, 1753–1762.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bhanja Chowdhury J., Shrivastava S., Steele R., Di Bisceglie A.M., Ray R., and Ray R.B. 2012. Hepatitis C virus infection modulates expression of interferon stimulatory gene IFITM1 by upregulating miR-130A. J. Virol. 86, 10221–10225.

    Article  PubMed Central  PubMed  Google Scholar 

  • Blight K.J. and Rice C.M. 1997. Secondary structure determination of the conserved 98-base sequence at the 3′ terminus of hepatitis C virus genome RNA. J. Virol. 71, 7345–7352.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bruni R., Marcantonio C., Tritarelli E., Tataseo P., Stellacci E., Costantino A., Villano U., Battistini A., and Ciccaglione A.R. 2011. An integrated approach identifies IFN-regulated micro-RNAs and targeted mRNAs modulated by different HCV replicon clones. BMC Genomics 12, 4–5.

    Article  Google Scholar 

  • Chen Y., Chen J., Wang H., Shi J., Wu K., Liu S., Liu Y., and Wu J. 2013. HCV-induced miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1. PLoS Pathogens 9, e1003248.

    Article  Google Scholar 

  • Cheng J.C., Yeh Y.J., Tseng C.P., Hsu S.D., Chang Y.L., Sakamoto N., and Huang H.D. 2012. Let-7b is a novel regulator of hepatitis C virus replication. Cell Mol. Life Sci. 69, 2621–2633.

    Article  CAS  PubMed  Google Scholar 

  • Conrad K.D., Giering F., Erfurth C., Neumann A., Fehr C., Meister G., and Niepmann M. 2013. MicroRNA-122 dependent binding of Ago2 protein to hepatitis C virus RNA is associated with enhanced RNA stability and translation stimulation. PLoS ONE 8, e56272.

    Article  Google Scholar 

  • Conrad K.D. and Niepmann M. 2014. The role of microRNA in hepatitis C virus RNA replication. Arch. Virol. 159, 849–862.

    Article  CAS  PubMed  Google Scholar 

  • Esquela-Kerscher A. and Slack F.J. 2006. Oncomirs-microRNAs with a role in cancer. Nat. Rev. Cancer 6, 259–269.

    Article  CAS  PubMed  Google Scholar 

  • Fabian M.R. and Sonenberg N. 2012. The mechanics of miRNA mediated gene silencing: a look under the hood of miRISC. Nat. Struct. Mol. Biol. 19, 586–593.

    Article  CAS  PubMed  Google Scholar 

  • Filipowicz W., Bhattacharyya S.N., and Sonenberg N. 2008. Mechanism of post-transcriptional regulation by microRNA: are the answers in sight? Nat. Rev. Genet. 9, 102–114.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Friebe P., Lohmann V., Krieger N., and Bartenschlager R. 2011. Sequences in the 5′nontranslated region of hepatitis C virus required for RNA replication. J. Virol. 75, 12047–12057.

    Article  Google Scholar 

  • Fried M.W., Shiffman M.L., Reddy K.R., Smith C., Marinos G., Goncales F.L. Jr., Häussinger D., Diago M., Carosi G., Dhumeaux D., and et al. 2002. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347, 975–982.

    Article  CAS  PubMed  Google Scholar 

  • Fukuhara T., Kambara H., Shiokawa M., Ono C., Katoh H., Morita E., Okuzaki D., Maehara Y., Koike K., and Matsuura Y. 2012. Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. J. Virol. 86, 7918–7933.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Georgel P., Schuster C., Zeisel M.B., Stoll-Keller F., Berg T., Bahram S., and Baumert T.F. 2010. Virus-host interactions in hepatitis C virus infection: implications for molecular pathogenesis and antiviral strategies. Trends Mol. Med. 16, 277–286.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Guo H., Ingolia N.T., Weissman J.S., and Bartel D.P. 2010. Mammalian microRNAs predominantly act to decrease target mRNA level. Nature 466, 835–840.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hafner M., Landthaler M., Burger L., Khorshid M., Hausser J., Berninger P., Rothballer A., Ascano M., Jungkamp A.C., Munschauer M., and et al. 2010. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PARCLIP. Cell 141, 129–141.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Han J., Lee Y., Yeom K.H., Kim Y.K., Jin H., and Kim V.N. 2004. The Drosha-DGCR8 complex in primary miRNA processing. Genes Dev. 18, 3016–3027.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henke J.I., Goergen D., Zheng J., Song Y., Schüttler C.G., Fehr C., Jünemann C., and Niepmann M. 2014. microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J. 27, 3300–3310.

    Article  Google Scholar 

  • Hoffmann T.W., Duverlie G., and Bengrine A. 2012. MicroRNAs and hepatitis C virus: toward the end of miR-122 supremacy. Virol. J. 9, 1–9.

    Article  Google Scholar 

  • Hoffman B. and Liu Q. 2011. Hepatitis C viral protein translation: mechanisms and implications in developing antivirals. Liver Int. 31, 1449–1467.

    Article  CAS  PubMed  Google Scholar 

  • Hou W., Tian Q., Zheng J., and Bonkovsky H.L. 2010. MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins. Hepatology 51, 1494–1504.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Huntzinger E. and Izaurralde E. 2011. Gene silencing by micro-RNAs: contributions of translational repression and mRNA decay. Nat. Rev. Genet. 12, 99–110.

    Article  CAS  PubMed  Google Scholar 

  • Ishida H., Tatsumi T., Hosui A., Nawa T., Kodama T., Shimizu S., Hikita H., Hiramatsu N., Kanto T., Hayashi N., and et al. 2011. Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway. Biochem. Biophys. Res. Commun. 412, 92–97.

    Article  CAS  PubMed  Google Scholar 

  • Janssen H.L., Reesink H.W., Lawitz E.J., Zeuzem S., Rodriguez-Torres M., Patel K., van der Meer A.J., Patick A.K., Chen A., Zhou Y., and et al. 2013. Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368, 1685–1694.

    Article  CAS  PubMed  Google Scholar 

  • Jopling C.L., Schutz S., and Sarnow P. 2008. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 4, 77–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jopling C.L., Yi M., Lancaster A.M., Lemon S.M., and Sarnow P. 2005. Modulation of hepatitis C virus RNA abundance by a liver specific microRNA. Science 309, 1577–1581.

    Article  CAS  PubMed  Google Scholar 

  • Kambara H., Fukuhara T., Shiokawa M., Ono C., Ohara Y., Kamitani W., and Matsuura Y. 2012. Establishment of a novel permissive cell line for the propagation of hepatitis C virus by expression of microRNA miR-122. J. Virol. 86, 1382–1393.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kieffer T.L., Kwong A.D., and Picchio G.R. 2010. Viral resistance to specifically targeted antiviral therapies for hepatitis C (STAT-Cs). J. Antimicrob. Chemother. 65, 202–212.

    Article  CAS  PubMed  Google Scholar 

  • Kim V.N. 2004. MicroRNA precursors in motion: Exportin-5 mediates their nuclear export. Trends Cell Biol. 14, 156–159.

    Article  CAS  PubMed  Google Scholar 

  • Kim C.W. and Chang K.M. 2013. Hepatitis C virus: virology and life cycle. Clin. Mol. Hepatol. 19, 17–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim V.N., Han J., and Siomi M.C. 2009. Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 10, 126–139.

    Article  CAS  PubMed  Google Scholar 

  • Kolykhalov A.A., Feinstone S.M., and Rice C.M. 1996. Identification of a highly conserved sequence element at the 3′ terminus of hepatitis C virus genome RNA. J. Virol. 70, 3363–3371.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kolykhalov A.A., Mihalik K., Feinstone S.M., and Rice C.M. 2000. Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3′untranslated regions are essential for virus replication in vivo. J. Virol. 74, 2046–2051.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee Y., Ahn C., Han J., Choi H., Kim J., Yim J., Lee J., Provost P., Radmark O., Kim S., and et al. 2003. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419.

    Article  CAS  PubMed  Google Scholar 

  • Lee Y., Jeon K., Lee J.T., Kim S., and Kim V.N. 2002. Micro-RNA maturation: stepwise processing and subcellular localization. EMBO J. 21, 4663–4670.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee C.H., Kim J.H., and Lee S.W. 2013. Prospects for nucleic acidbased therapeutics against hepatitis C virus. World J. Gastroenterol. 19, 8949–8962.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li S., Duan X., Li Y., Liu B., McGilvray I., and Chen L. 2013a. MicroRNA-130a inhibits HCV replication by restoring the innate immune response. J. Viral Hepatit. 21, 121–128.

    Article  CAS  Google Scholar 

  • Li Y., Masaki T., Yamane D., McGivern D.R., and Lemon S.M. 2013b. Competing and noncompeting activities of miR-122 and the 5′exonuclease Xrn1 in regulation of hepatitis C virus replication. Proc. Natl. Acad. Sci. USA 110, 1881–1886.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liang Y., Ridzon D., Wong L., and Chen C. 2007. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8, 1–6.

    Article  Google Scholar 

  • Liu X., Wang T., Wakita T., and Yang W. 2010. Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology 398, 57–67.

    Article  CAS  PubMed  Google Scholar 

  • Liu Y., Wimmer E., and Paul A.V. 2009. Cis-acting RNA elements in human and animal plus-strand RNA viruses. Biochim. Biophys. Acta. 1789, 495–517.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lohmann V. 2013. Hepatitis C virus RNA replication. Curr. Top. Microbiol. Immunol. 369, 167–198.

    CAS  PubMed  Google Scholar 

  • Machlin E.S., Sarnow P., and Sagan S.M. 2011. Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex. Proc. Natl. Acad. Sci. USA 108, 3193–3198.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marquez R.T., Bandyopadhyay S., Wendlandt E.B., Keck K., Hoffer B.A., Icardi M.S., Christensen R.N., Schmidt W.N., and McCaffrey A.P. 2010a. Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans. Lab. Invest. 90, 1727–1736.

    Article  CAS  PubMed  Google Scholar 

  • Marquez R.T., Wendlandt E., Galle C.S., Keck K., and McCaffrey A.P. 2010b. MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-kappaB signaling. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G535–G541.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moradpour D., Penin F., and Rice C.M. 2007. Replication of hepatitis C virus. Nat. Rev. Microbiol. 5, 453–463.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Murakami Y., Toyoda H., Tanaka M., Kuroda M., Harada Y., Matsuda F., Tajima A., Kosaka N., Ochiya T., and Shimotohno K. 2011. The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families. PLoS ONE 6, e16081.

    Article  Google Scholar 

  • Narbus C.M., Israelow B., Sourisseau M., Michta M.L., Hopcraft S.E., Zeiner G.M., and Evans M.J. 2011. HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle. J. Virol. 85, 12087–12092.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nasheri N., Singaravelu R., Goodmurphy M., Lyn R.K., and Pezacki J.P. 2011. Competing roles of microRNA-122 recognition elements in hepatitis C virus RNA. Virology 410, 336–344.

    Article  CAS  PubMed  Google Scholar 

  • Niepmann M. 2009. Activation of hepatitis C virus translation by a liver specific microRNA. Cell Cycle 8, 1473–1477.

    Article  CAS  PubMed  Google Scholar 

  • Niepmann M. 2013. Hepatitis C virus RNA translation. Curr. Top. Microbiol. Immunol. 369, 143–166.

    CAS  PubMed  Google Scholar 

  • Ogawa T., Enomoto M., Fujii H., Sekiya Y., Yoshizato K., Ikeda K., and Kawada N. 2012. MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut 61, 1600–1609.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pietschmann T. 2009. Regulation of hepatitis C virus replication by microRNAs. J. Hepatol. 50, 441–444.

    Article  CAS  PubMed  Google Scholar 

  • Pineau P., Volinia S., McJunkin K., Marchio A., Battiston C., Terris B., Mazzaferro V., Lowe S.W., Croce C.M., and Dejean A. 2010. miR-221 overexpression contributes to liver tumorigenesis. Proc. Natl. Acad. Sci. USA 107, 264–269.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Raimondi S., Bruno S., Mondelli M.U., and Maisonneuve P. 2009. Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J. Hepatol. 50, 1142–1154.

    Article  CAS  PubMed  Google Scholar 

  • Roberts A.P., Lewis A.P., and Jopling C.L. 2011Sa. miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res. 39, 7716–7729.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roberts A.P., Lewis A.P., and Jopling C.L. 2011b. The role of microRNAs in viral infection. Prog. Mol. Biol. Transl. Sci. 102, 101–139.

    Article  CAS  PubMed  Google Scholar 

  • Sarnow P., Jopling C.L., Norman K.L., Schütz S., and Wehner K.A. 2006. MicroRNAs: expression, avoidance and subversion by vertebrate viruses. Nat. Rev. Microbiol. 4, 651–659.

    Article  CAS  PubMed  Google Scholar 

  • Scagnolari C., Zingariello P., Vecchiet J., Selvaggi C., Racciatti D., Taliani G., Riva E., Pizzigallo E., and Antonelli G. 2010. Differential expression of interferon-induced microRNAs in patients with chronic hepatitis C virus infection treated with pegylated interferon alpha. Virol. J. 7, 3–1.

    Article  Google Scholar 

  • Shimakami T., Yamane D., Jangra R.K., Kempf B.J., Spaniel C., Barton D.J., and Lemon S.M. 2012a. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc. Natl. Acad. Sci. USA 109, 941–946.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shimakami T., Yamane D., Welsch C., Hensley L., Jangra R.K., and Lemon S.M. 2012b. Base pairing between hepatitis C virus RNA and microRNA 122 3′ of its seed sequence is essential for genome stabilization and production of infectious virus. J. Virol. 86, 7372–7383.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shirasaki T., Honda M., Shimakami T., Horii R., Yamashita T., Sakai Y., Sakai A., Okada H., Watanabe R., Murakami S., and et al. 2013. MicroRNA-27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells. J. Virol. 87, 5270–5286.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shwetha S., Gouthamchandra K., Chandra M., Ravishankar B., Khaja M.N., and Das S. 2013. Circulating miRNA profile in HCV infected serum: novel insight into pathogenesis. Sci. Rep. 3, 15–5.

    Article  Google Scholar 

  • Singaravelu R., Chen R., Lyn R.K., Jones D.M., O’Hara S., Rouleau Y., Cheng J., Srinivasan P., Nasheri N., Russell R.S., and et al. 2013. Hepatitis C virus induced up-regulation of microRNA-27: A novel mechanism for hepatic steatosis. Hepatology 59, 98–108.

    Article  PubMed  Google Scholar 

  • Stefani G. and Slack F.J. 2008. Small non-coding RNAs in animal development. Nat. Rev. Mol. Cell Biol. 9, 219–230.

    Article  CAS  PubMed  Google Scholar 

  • Steuerwald N.M., Parsons J.C., Bennett K., Bates T.C., and Bonkovsky H.L. 2010. Parallel microRNA and mRNA expression profiling of (genotype 1b) human hepatoma cells expressing hepatitis C virus. Liver Int. 30, 1490–1504.

    Article  CAS  PubMed  Google Scholar 

  • Takamizawa A., Mori C., Fuke I., Manabe S., Murakami S., Fujita J., Onishi E., Andoh T., and Okayama H. 1991. Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol. 65, 1105–1113.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takaoka A. and Yanai H. 2006. Interferon signaling network in innate defence. Cell Microbiol. 8, 907–922.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Vassilaki N., Friebe P., Meuleman P., Kallis S., Kaul A., Paranhos-Baccala G., Leroux-Roels G., Mavromara P., and Bartenschlager R. 2008. Role of the hepatitis C virus core +1 open reading frame and core cis-acting RNA elements in viral RNA translation and replication. J. Virol. 82, 11503–11515.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson J.A., Zhang C., Huys A., and Richardson C.D. 2011. Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. J. Virol. 85, 2342–2350.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Winter J., Jung S., Keller S., Gregory R.I., and Diederichs S. 2009. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat. Cell Biol. 11, 228–234.

    Article  CAS  PubMed  Google Scholar 

  • Witwer K.W., Sisk J.M., Gama L., and Clements J.E. 2010. Micro-RNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune reponse. J. Immunol. 184, 2369–2376.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yi M. and Lemon S.M. 2003. 3′ untranslated RNA signals required for replication of hepatitis C virus RNA. J. Virol. 77, 3557–3568.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yoshikawa T., Takata A., Otsuka M., Kishikawa T., Kojima K., Yoshida H., and Koike K. 2012. Silencing of microRNA-122 enhances interferon-alpha signaling in the liver through regulating SOCS3 promoter methylation. Sci. Rep. 2, 6–7.

    Article  Google Scholar 

  • Zampino R., Marrone A., Restivo L., Guerrera B., Sellitto A., Rinaldi L., Romano C., and Adinolfi L.E. 2013. Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations. World J. Hepatol. 5, 528–540.

    PubMed Central  PubMed  Google Scholar 

  • Zeng B., Li Z., Chen R., Guo N., Zhou J., Zhou Q., Lin Q., Cheng D., Liao Q., Zheng L., and et al. 2012. Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3. FEBS Lett. 586, 3271–3278.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X., Daucher M., Armistead D., Russell R., and Kottilil S. 2013. MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-α. PLoS ONE 8, e55733.

    Article  Google Scholar 

  • Zhang C., Huys A., Thibault P.A., and Wilson J.A. 2012a. Requirements for human Dicer and TRBP in microRNA-122 regulation of HCV translation and RNA abundance. Virology 433, 479–488.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y., Wei W., Cheng N., Wang K., Li B., Jiang X., and Sun S. 2012b. Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology 56, 1631–1640.

    Article  CAS  PubMed  Google Scholar 

  • Zheng F., Liao Y.J., Cai M.Y., Liu Y.H., Liu T.H., Chen S.P., Bian X.W., Guan X.Y., Lin M.C., Zeng Y.X., and et al. 2012. The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2. Gut 61, 278–289.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chang Ho Lee or Seong-Wook Lee.

Additional information

Lee CH, Kim JH, and Lee SW designed this study, collected all the data, and wrote the manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, C.H., Kim, J.H. & Lee, SW. The role of microRNAs in Hepatitis C Virus replication and related liver diseases. J Microbiol. 52, 445–451 (2014). https://doi.org/10.1007/s12275-014-4267-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-014-4267-x

Keywords

Navigation