Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2018; 24(2): 226-236
Published online Jan 14, 2018. doi: 10.3748/wjg.v24.i2.226
Hepatitis C virus core protein-induced miR-93-5p up-regulation inhibits interferon signaling pathway by targeting IFNAR1
Chang-Long He, Ming Liu, Zhao-Xia Tan, Ya-Jun Hu, Qiao-Yue Zhang, Xue-Mei Kuang, Wei-Long Kong, Qing Mao
Chang-Long He, Ming Liu, Zhao-Xia Tan, Ya-Jun Hu, Qiao-Yue Zhang, Xue-Mei Kuang, Wei-Long Kong, Qing Mao, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
Chang-Long He, Ming Liu, Zhao-Xia Tan, Ya-Jun Hu, Qiao-Yue Zhang, Xue-Mei Kuang, Wei-Long Kong, Qing Mao, Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400037, China
Author contributions: All authors contributed to the manuscript.
Supported by National Natural Science Foundation of China, No. 81371849; and the TMMU Key Project for Clinical Research, No. 2012XLC05.
Institutional review board statement: This study was approved by the Ethics Committee of the First Affiliated Hospital of Third Military Medical University.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article are reported.
Data sharing statement: No additional data are available.
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: Qing Mao, MD, PhD, Doctor, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Chongqing 400037, China. qingmao@tmmu.edu.cn
Telephone: +86-23-68754858 Fax: +86-23-68754858
Received: October 26, 2017
Peer-review started: October 27, 2017
First decision: November 21, 2017
Revised: December 5, 2017
Accepted: December 13, 2017
Article in press: December 13, 2017
Published online: January 14, 2018
ARTICLE HIGHLIGHTS
Research background

Hepatitis C virus (HCV)-1b core protein is an important component of HCV and plays a crucial role in HCV infection and pegylated IFNα resistance, but the mechanism underlying HCV core protein-induced pegylated IFNα resistance remains unclear.

Research motivation

Our findings highlight the mechanism that HCV-1b core protein induces pegylated IFNα resistance via regulating the miR-93-5p-interferon receptor 1 (IFNAR1) axis. This axis may be a potential therapeutic target for HCV-1b treatment.

Research objectives

The objective of this study was to elucidate why HCV-1b causes pegylated IFNα resistance. It is partially realized and provides a clue for drug design of HCV-1b treatment.

Research methods

The research methods included cell culture, RNA extraction, qRT-PCR, vector construct, oligonucleotide transfection, luciferase assay, and Western blot. Data analysis was performed using multiple statistical methods that include the Mann-Whitney test, two-tailed Student’s t-test, one-way ANOVA, and Pearson’s correlation. Eighty-four patients with HCV-1b infection and 84 healthy subjects were enrolled in this study.

Research results

This study found that serum miR-93-5p expression was increased in patients with HCV-1b infection and HCV-1b core protein increased miR-93-5p expression, identified that IFNAR1 is a target of miR-93-5p, and further demonstrated that the miR-93-5p-IFNAR1 axis regulated the IFN signaling pathway.

Research conclusions

This study found that HCV-1b increases miR-93-5p expression, IFNAR1 is a target of miR-93-5p in hepatocyte, and miR-93-5p-IFNAR1 axis regulates the IFN signaling pathway. This study also provided some evidence that HCV-1b induces pegylated IFNα resistance by regulating the miR-93-5p-IFNAR1 axis, suggesting that the miR-93-5p-IFNAR1 axis might be a potential therapeutic target for HCV-1b infection.

Research perspectives

This study demonstrated the mechanism by which miR-93-5p inhibits the IFN signaling pathway in vitro, but an in vitro study needs to be performed in the future. The design of siRNAs which exclusively destroy the miR-93-5p-IFNAR1 axis may be important for improving the therapeutic effect of pegylated IFNα.