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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2016; 22(4): 1487-1496
Published online Jan 28, 2016. doi: 10.3748/wjg.v22.i4.1487
MicroRNA-mediated interactions between host and hepatitis C virus
Hu Li, Jian-Dong Jiang, Zong-Gen Peng
Hu Li, Jian-Dong Jiang, Zong-Gen Peng, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Jian-Dong Jiang, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Author contributions: All the authors contributed to the search and analysis of literature and to the manuscript preparation.
Supported by National Natural Science Foundation of China No. 81321004 and No. 81322050; National Mega-Project for “R&D for Innovative Drugs”, Ministry of Science and Technology, China No. 2012ZX09301-002-001; and Ministry of Education, China No. NCET-12-0072.
Conflict-of-interest statement: The authors declare no conflicts of interest in this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zong-Gen Peng, PhD, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantan Xili, Beijing 100050, China. pumcpzg@126.com
Telephone: +86-10-63166129 Fax: +86-10-63017302
Received: July 20, 2015
Peer-review started: July 27, 2015
First decision: September 11, 2015
Revised: September 25, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: January 28, 2016
Abstract

MicroRNAs (miRNAs) are small noncoding RNAs. More than 2500 mature miRNAs are detected in plants, animals and several types of viruses. Hepatitis C virus (HCV), which is a positive-sense, single-stranded RNA virus, does not encode viral miRNA. However, HCV infection alters the expression of host miRNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host miRNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular mRNAs. Increasing evidence demonstrates that miRNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host mRNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host miRNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special miRNAs are closely correlated with liver-specific disease progression and the changed levels of miRNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCV-infected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.

Keywords: MicroRNAs, Hepatitis C virus, Host-virus interaction, Biomarker, Therapeutic targets

Core tip: Hepatitis C virus (HCV) infection changes the expression of host miRNAs in vitro and in vivo, while host MicroRNAs (miRNAs) in turn regulate HCV life cycle through directly binding to HCV RNA and/or indirectly targeting cellular mRNAs. The miRNA-centered competitive viral and host RNA network displays a cross-regulation pattern between host mRNAs and HCV genome. Evidence based on the miRNA-mediated host/viral interactions suggests that specific miRNAs can serve as novel diagnostic/prognostic biomarkers in HCV-infected patients with liver diseases and therapeutic targets for development of anti-HCV agents in the future.