Functional elucidation of miR-494 in modulation of HCV infection

Abstract Hepatitis C virus (HCV) infection is considered one of the most important causes of chronic liver diseases due to major alteration in the cross-talk between hepatic cells and immune cells. Many reports have shown that the proteins of HCV might interact with the genes to regulate cellular pathways and miRNA expression contribute to the pathogenesis of liver diseases. In this study, the profiling of miRNAs in hepatocytes transfected with HCV structure proteins was compared by microarray analysis. MiR-494 was significantly decreased in E1 transfected HepG2 cells, but increase in core-transfected or E2-transfected HepG2 cells. However, the expression and activation of TLR7/8 and inflammatory cytokines were dramatically enhanced by E1 protein. Interferon treatment was demonstrated to enhance miR-494 expression but reduced TLR7 and TLR8 signaling in E1 protein transfected HepG2. MiR-494 was proposed to regulate TLR7 and TLR8 expression as confirmed by directly targeting 3′-UTR of TLR7 and TLR8. However, the molecular functions of the involvement of miR-494 in HCV infected hepatocytes remained to be elucidated. The expression of miR-494 in serum samples of HCV infected patients was increased as compared with corresponding controls (mean ± SEM: 23,100 ± 9,700 vs.32.5± 14.2, p< 0.001). Determined through analysis using XTT and transwell assays, the HCV core-overexpression and miR-494 restoration were demonstrated to significantly enhance HepG2 proliferation and migration, In conclusion, our results have shown that HCV structure proteins might play a role in the pathogenesis of chronic hepatic diseases via interaction with miRNA-494 to modulate TLR7/8 expression.