Published online Jan 14, 2018. doi: 10.3748/wjg.v24.i2.226
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
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.
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.
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.
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.
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.
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.
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.