MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-?.

ABSTRACT: Increasing evidence suggests that miRNAs have a profound impact on host defense to Hepatitis C virus (HCV) infection and clinical outcome of standard HCV therapy. In this study, we investigated modulation of miRNA expression in Huh7.5 hepatoma cells by HCV infection and in vitro interferon-?treatment.MiRNA expression profiling was determined using Human miRNA TaqMan® Arrays followed by rigorous pairwise statistical analysis. MiRNA inhibitors assessed the functional effects of miRNAs on HCV replication. Computational analysis predicted anti-correlated mRNA targets and their involvement in host cellular pathways. Quantitative RTPCR confirmed the expression of predicted miRNA-mRNA correlated pairs in HCV-infected Huh7.5 cells with and without interferon-?.Seven miRNAs (miR-30b, miR-30c, miR-130a, miR-192, miR-301, miR-324-5p, and miR-565) were down-regulated in HCV-infected Huh7.5 cells (p<0.05) and subsequently up-regulated following interferon-? treatment (p<0.01). The miR-30(a-d) cluster and miR-130a/301 and their putative mRNA targets were predicted to be associated with cellular pathways that involve Hepatitis C virus entry, propagation and host response to viral infection.HCV differentially modulates miRNAs to facilitate entry and early establishment of infection in vitro. Interferon-? appears to neutralize the effect of HCV replication on miRNA regulation thus providing a potential mechanism of action in eradicating HCV from hepatocytes.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC3572124 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature