MicroRNA-let-7c suppresses hepatitis C virus replication by targeting Bach1 for induction of haem oxygenase-1 expression.

MicroRNAs are small noncoding RNAs that are central factors between hepatitis C virus (HCV) and host cellular factors for viral replication and liver disease progression, including liver fibrosis, cirrhosis and hepatocellular carcinoma. In the present study, we found that overexpressing miR-let-7c markedly reduced HCV replication because it induced haem oxygenase-1 (HO-1) expression by targeting HO-1 transcriptional repressor Bach1, ultimately leading to stimulating an antiviral interferon response and blockade of HCV viral protease activity. In contrast, the antiviral actions of miR-let-7c were attenuated by miR-let-7c inhibitor treatment, exogenously expressing Bach1 or suppressing HO-1 activity and expression. A proposed model indicates a key role for miR-let-7c targeting Bach1 to transactivate HO-1-mediated antiviral actions against HCV. miR-let-7c may serve as an attractive target for antiviral development.