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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2015; 21(24): 7375-7399
Published online Jun 28, 2015. doi: 10.3748/wjg.v21.i24.7375
Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases
Jason Lamontagne, Laura F Steel, Michael J Bouchard
Jason Lamontagne, Microbiology and Immunology Graduate Program, Graduate School of Biomedical Sciences and Professional Studies, Drexel University College of Medicine, Philadelphia, PA 19102, United States
Laura F Steel, Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, United States
Michael J Bouchard, Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PA 19102, United States
Author contributions: Lamontagne J, Steel LF, and Bouchard MJ solely contributed to this paper.
Supported by Pennsylvania state CURE grant, No. 4100057658, [to Steel LF and Bouchard MJ (partially)]; and a Ruth L Kirschstein (F31) Predoctoral Fellowship, No. 5F31CA171712-03, [to Lamontagne J (partially)].
Conflict-of-interest: The authors report no conflicts of interest.
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: Michael J Bouchard, PhD, Department of Biochemistry, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA 19102, United States. michael.bouchard@drexelmed.edu
Telephone: +1-866-373-9352
Received: January 15, 2015
Peer-review started: January 15, 2015
First decision: March 10, 2015
Revised: March 25, 2015
Accepted: May 20, 2015
Article in press: May 21, 2015
Published online: June 28, 2015
Abstract

Chronic infection with the hepatitis B virus (HBV) is the leading risk factor for the development of hepatocellular carcinoma (HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, microRNAs (miRNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of miRNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between miRNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some miRNAs, such as miR-122, and miR-125 and miR-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and miRNAs, including how HBV affects cellular miRNAs, how these miRNAs impact HBV replication, and the relationship between HBV-mediated miRNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and miRNAs, and propose potential applications of miRNA-related techniques that could enhance our understanding of the role miRNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes.

Keywords: Hepatitis B virus, MicroRNA, Hepatocellular carcinoma, Hepatitis B virus replication

Core tip: In this review, we discuss the current state of our understanding of how hepatitis B virus (HBV) affects the expression profile of cellular microRNAs (miRNAs), how these miRNAs impact HBV replication, and the relationship between HBV-mediated miRNA regulation and hepatocellular carcinoma development. Importantly, we address challenges in studying the relationship between HBV and miRNAs, including the lack of an experimental system that effectively models HBV infection and a reliance on the use of transformed cell lines. Finally, we propose applications of techniques to address the functional impact of HBV-mediated regulation of miRNA expression, which could enhance our understanding of the role miRNAs play in HBV replication and disease.