Oncotarget

Research Papers:

Circulating microRNA-636 is associated with the elimination of hepatitis C virus by ombitasvir/paritaprevir/ritonavir

Asahiro Morishita _, Hirohito Yoneyama, Hisakazu Iwama, Koji Fujita, Miwako Watanabe, Kayo Hirose, Tomoko Tadokoro, Kyoko Oura, Teppei Sakamoto, Shima Mimura, Takako Nomura, Makoto Oryu, Takashi Himoto, Kunitada Shimotohno and Tsutomu Masaki

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Oncotarget. 2018; 9:32054-32062. https://doi.org/10.18632/oncotarget.25889

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Abstract

Asahiro Morishita1, Hirohito Yoneyama1, Hisakazu Iwama2, Koji Fujita1, Miwako Watanabe1, Kayo Hirose1, Tomoko Tadokoro1, Kyoko Oura1, Teppei Sakamoto1, Shima Mimura1, Takako Nomura1, Makoto Oryu3, Takashi Himoto4, Kunitada Shimotohno5 and Tsutomu Masaki1

1Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan

2Life Science Research Center, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan

3Department of Internal Medicine, Kagawa Saiseikai Hospital, Tahikamimachi, Takamatsu, Kagawa 761-8076, Japan

4Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan

5Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Kohnodai, Ichikawa, Chiba 272-8516, Japan

Correspondence to:

Asahiro Morishita, email: asahiro@med.kagawa-u.ac.jp

Keywords: circulating microRNA; microRNA-636; ombitasvir/paritaprevir/R; HCV elimination; direct-acting antiviral

Received: May 22, 2018     Accepted: July 13, 2018     Published: August 10, 2018

ABSTRACT

Hepatitis C virus (HCV) infection causes sustained inflammation and fibrosis. Several oral direct-acting antivirals (DAAs) including ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) were recently developed for HCV elimination. The combination of DAAs brought a higher sustained viral response (SVR) rate to anti-HCV therapy compared to interferon (IFN)-based regimens. However, 5% of hepatitis C patients who undergo DAA therapy still suffer from a sustained HCV infection. MicroRNA (miRNA) is essentially interfering, endogenous noncoding RNA that has been investigated as a new biomarker for the response to DAA in hepatitis C patients. Here we used a miRNA array and real-time polymerase chain reaction (PCR) to determine the targetable miRNA before and 12 weeks after OBV/PTV/r treatment for refractory hepatitis C. We used replicon cells, in which genotype 1b type HCV is stably transfected in Huh7 cells, to determine whether miRNA can inhibit HCV replication. Among 2,555 miRNAs, three were significantly up-regulated and eight miRNAs were down-regulated in serum 12 weeks after OBV/PTV/r treatment. An unsupervised hierarchical clustering analysis, using Pearson's correlation, showed that the miRNA profiles between before and 12 weeks after OBV/PTV/r treatment were clustered separately. At 12 weeks after OBV/PTV, miR-636 was targeted among the eight down-regulated miRNAs, and the expression level of circulating miR-636 was significantly diminished. The amount of HCV-RNA was significantly diminished 48 hours after miR-636 inhibitor transfection in HCV replicon cells. In conclusion, miR-636 might be one of the essential targetable molecules in HCV patients who undergo DAA therapy and still suffer from a sustained HCV infection.


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