Oncotarget

Research Papers:

Screening of microRNAs for a repressor of hepatitis B virus replication

Yutaka Naito, Susumu Hamada-Tsutsumi, Yusuke Yamamoto, Akiko Kogure, Yusuke Yoshioka, Koichi Watashi, Takahiro Ochiya and Yasuhito Tanaka _

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Oncotarget. 2018; 9:29857-29868. https://doi.org/10.18632/oncotarget.25557

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Abstract

Yutaka Naito1,*, Susumu Hamada-Tsutsumi2,*, Yusuke Yamamoto1, Akiko Kogure1, Yusuke Yoshioka1, Koichi Watashi3, Takahiro Ochiya1 and Yasuhito Tanaka2

1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan

2Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

3Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan

*These authors have contributed equally to this work

Correspondence to:

Yasuhito Tanaka, email: ytanaka@med.nagoya-cu.ac.jp

Keywords: hepatitis B virus; microRNA; miR-204; Rab22a

Received: October 27, 2017    Accepted: May 13, 2018    Published: July 06, 2018

ABSTRACT

Background: Hepatitis B virus (HBV) infection is a leading cause of persistent liver diseases, cirrhosis and hepatocellular carcinoma (HCC) worldwide. Since deregulation of microRNA (miRNA) expression by HBV infection contributes to enhanced viral replication and pathogenesis, modulation of miRNA activity can be a novel therapeutic approach towards HBV eradication. As the effects of the vast majority of miRNAs on HBV replication have not been empirically investigated, here, we aim to identify novel therapeutic targets that have a strong antiviral effect on HBV.

Methods: HepG2-hNTCP-C4 cells were infected with HBV, and then were individually transfected with the library mimics of 2048 miRNAs. To assess the amount of intracellular and extracellular DNA and HBsAg, qPCR and ELISA were performed respectively.

Results: From miRNA library screening, we identified 39 miRNAs as candidate repressors of HBV replication. Among them, 9 miRNAs, including miR-204, strongly decreased both HBV DNA and HBsAg in culture supernatant of HepG2-hNTCP-C4 cells. Furthermore, we also showed that inhibition of Rab22a, one of the targets of miR-204, also suppressed intracellular and extracellular HBV DNA expression in HepG2.2.15.7 cells.

Conclusions: Our findings contribute to the understanding of the roles of miRNAs underlying HBV replication and show the possibility of developing a novel strategy for miRNA-mediated HBV treatment.


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