The Role of MicroRNAs in Response to Interferon Treatment of Chronic Hepatitis C patients
Keywords:
microRNA, Interferon, Chronic Hepatitis C, HCV, pegylated interferonAbstract
ntroduction: Treatment of HCV using a combination of pegylated interferon (PEG-IFN) and ribavirin fails in about 40% of the patients with HCV genotype 4 infections, and it is physically and economically demanding. Thus, it is highly important to identify factors that can help to predict the likelihood that a patient will respond to this treatment.
Methods: In this study, five miRNAs, i.e., miRNA-122, miRNA-199, miRNA-192, miRNA-30, and miRNA-128, were selected according to previous studies that demonstrated their noticeable functions in viral replication, indicating that they potentially could be used by host cells to control viral infections. The five miRNAs were measured using real-time, reverse transcription-polymerase chain reactions. The data were analyzed using the t-test and chi-squared test.
Results: We found that the expression level of miRNA-122 was significantly increased in the responders’ group (p < 0.01) over that in the non-responders’ groups before and after treatment; both increased significantly (p < 0.01) compared with the normal control group.
Conclusion: miR-122 might be a useful predictor for virological responses to treatment with PEG-interferon plus ribavirin therapy in patients with HCV.
References
Kwon YC, Ray RB, Ray R. Hepatitis C virus infection: establishment of chronicity and liver disease
progression. EXCLI J. 2014; 13: 977-96. PMID: 26417315, PMCID: PMC4464452.
Asselah T, Benhamou Y, Marcellin P. Protease and polymerase inhibitors for the treatment of hepatitis C.
Liver Int. 2009; 29: 57-67. doi: 10.1111/j.1478-3231.2008.01928.x, PMID: 19207967.
Yuan Li, Yuan J, Yujia Li, Shilin Li, Duan X, Liu B, et al. Host factors to predict treatment response in
HCV patients: Implications for individualized therapy and translational medicine for HCV. J Bioanal
Biomed. 2013; 5: 4-6.
Davidson-Moncada J, Papavasilion FN, Tam W. Micro RNAs of the immune system: roles of inflammation
and cancer. Ann N Y Acad Sci. 2010; 1183: 183-94. doi: 10.1111/j.1749-6632.2009.05121.x, PMID:
, PMCID: PMC2876712.
Liu X, Wang T, Wakita T, Yang W. Systematic identification of micro RNA and messenger RNA profiles
in hepatitis C virus-infected human hepatoma cells. Virology. 2010; 398: 57-67. doi:
1016/j.virol.2009.11.036, PMID: 20006370.
Gelley F, Zadori G, Nemes B, Fassan M, lendvai G, Sarvary E, et al. Micro RNA profile before and after
antiviral therapy in liver transplant recipients for hepatitis C virus cirrhosis. J Gastroenterol Hepatol. 2014;
: 121-7. doi: 10.1111/jgh.12362, PMID: 24033414.
Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific
micrornas from mouse. Curr Biol. 2002; 12: 735-9. doi: 10.1016/S0960-9822(02)00809-6.
Neilson JR, Zheng GX, Burge CB, Sharp PA. Dynamic regulation of miRNA expression in ordered stages
of cellular development. Genes Dev. 2007; 21: 578-89. doi: 10.1101/gad.1522907, PMID: 17344418,
PMCID: PMC1820899.
Berkhout B. A balancing act: viruses and miRNAs. J Formos Med Assoc. 2008; 107: 1-3. doi:
1016/S0929-6646(08)60001-7.
Haybaeck J, Zeller N, Heikenwalder M. The parallel universe: micro RNAs and their role in chronic
hepatitis, liver tissue damage and hepatocarcinogenesis. European journal of medical sciences. 2011; 141:
-90.
Motawi TM, Rizk SM, Shaker OG, Mokhtar OZH. Micro RNAs predictor markers for response to
interferon treatment of chronic hepatitis C genotype-4 in Egyptian patients. PLoS ONE. 2015; 10(3): 1371- 93.
Hoffmann TW, Gilles D, Bengrine A. Micro RNAs and hepatitis C virus: Toward the end of miR-122
supremacy. Virol J. 2012; 9: 109-16. doi: 10.1186/1743-422X-9-109, PMID: 22691570, PMCID:
PMC3489824.
Murakami Y, Tanaka M, Toyoda H, Hayashi K, Kuroda M, Tajima A, et al. Hepatic micro RNA
expression is associated with the response to interferon treatment of chronic hepatitis C. BMC Med
Genomics. 2010; 3: 48-57. doi: 10.1186/1755-8794-3-48, PMID: 20969775, PMCID: PMC2984584.
Zhang X, Daucher M, Armistead D, russel R, Kottilil Sh. Micro RNA expression profiling in HCV-infected
human hepatoma cells identifies potential anti-viral targets induced by interferon-α. Plos One. 2013; 8(2):
e55733. doi: 10.1371/journal.pone.0055733, PMID: 23418453, PMCID: PMC3572124.
Shwetha S, Gouthamchandra K, Chandra M, Ravishankar B, Khaja M, Das S. Circulating miRNA profile
in HCV infected serum: novel insight into pathogenesis. Scientific Reports. 2013; (3): 1-7. doi:
1038/srep01555.
Roy S, Benz F, Ludde T, Roderburg C. The role of miRNAs in the regulation of inflammatory processes
during hepatofibrogenesis. Hepatobiliary Surg Nutr. 2015; 4(1): 24-33. doi: 10.3978/j.issn.2304- 3881.2015.01.05, PMID: 25713802, PMCID: PMC4318955.
Su T, Liu CH, Liu CJ, Chen C, Ting T, Tseng T, et al. Serum microRNA-122 level correlates with
Virologic responses to pegylated interferon therapy in chronic hepatitis C. proc Natl Acad Sci. 2013;
(19): 7844-9. doi: 10.1073/pnas.1306138110, PMID: 23613588, PMCID: PMC3651447.
Page A, Mann D, Mann J. The mechanisms of HSC activation and epigenetic regulation of HSCs
phenotypes. Curr Pathobiol Res. 2014; (2): 163-70. doi: 10.1007/s40139-014-0052-0.
Pedersen IM, Cheng G, Wieland S. Interferon modulation of cellular microRNAs as an antiviral
mechanism. Nature. 2007; 449: 919-22. doi: 10.1038/nature06205, PMID: 17943132, PMCID:
PMC2748825.
Shrivastava Sh, Steele R, Ray R, Ray RB. MicroRNAs: Role in hepatitis C virus pathogenesis. Genes and
Diseases. 2015; 2(1): 35-45. doi: 10.1016/j.gendis.2015.01.001.
Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH, Filipowicz W. Decreased levels of micro RNA
miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med. 2009; 15: 31-33.
doi: 10.1038/nm.1902, PMID: 19122656.
Shrivastava Sh, Mukherjee A, Ray R. hepatitis C virus infection, microRNA and liver disease progression.
World J Hepatol. 2013; 5(9): 479-86. PMID: 24073299, PMCID: PMC3782685.
Nasheri N, Singaravelu R, Goodmurphy M, Lyn PK, Pezacki JP. Competing roles of micro RNA-122
recognition elements in hepatitis C virus RNA. Virology. 2011; 410: 336-44. doi:
1016/j.virol.2010.11.015, PMID: 21185047.
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
