Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5

PURPOSE: Hepatitis C virus (HCV) poses a risk of chronic liver disease and threatens a significant number of people worldwide. MicroRNAs (miRNAs) are linked to the regulation of hepatocarcinogenesis. Although miR-373 is required for HCV infection, the underlying mechanisms of miR-373 involvement in HCV replication remain elusive. MATERIALS AND METHODS: Quantitative reverse transcription PCR assays were performed to detect the abundances of miR-373 and HCV RNA either in Huh 7.5 cells or liver biopsy specimens with HCV infection. Luciferase assay was employed to probe the interactions between miR-373 and interferon regulatory factor 5 (IRF5). Western blot was conducted to investigate the effect of miR-373 and IRF5 on HCV replication and activation of type 1 interferon (IFN) response in JFH1-infected Huh 7.5 cells. RESULTS: HCV infection appeared to be caused by increased miR-373 expression. Addition of miR-373 promoted HCV RNA expression, while miR-373 depletion led to an inhibitive effect on HCV replication. Concordantly, IRF5, as a direct target, was limited by miR-373 in JFH1-infected Huh 7.5 cells. In addition, introduction of IRF5 protected HCV replication in the presence of abundant miR-373. Furthermore, the miR-373-mediated inhibitory effect on type 1 IFN response was ablated following IRF5 accumulation. CONCLUSION: miR-373 abrogation reduced HCV replication via activation of type 1 IFN responses by targeting IRF5 in JFH1-infected Huh 7.5 cells, suggesting a promising therapeutic for treating HCV infection.

Association of Interleukin-6 Gene-174C/G and-572C/G Polymorphisms with Hypertension:A Meta-Analysis / 现代检验医学杂志

Objective To assess the association of interleukin-6 (IL-6)-174C/G and-572C/G gene polymorphisms with hy-pertension risk.Methods The electronic databases,such as Pubmed,Web of Science,Google scholar,China National Knowl-edge Infrastrure and Wanfang database were searched by the interleukin-6,polymorphism,IL-6,hypertension,high blood pressure as the keywords/abstract.Random effect model was used to calculate the pooled odds ratio.Results The meta-a-nalysis included 6 studies with 1 041 hypertension cases and 1 088 health subjects,which was no significant association be-tween IL-6-174C/G gene polymorphism and hypertension (C vs G:OR=0.50,95%CI=0.22~ 1.14,P =0.10),and in the stratified analysis by ethnicity,no significant was found in Asian subgroup (C vs G:OR=0.75,95%CI=0.41~1.38,P =0.36).There was also no association between IL-6-572C/G gene polymorphism and hypertension in Asian (C vs G:OR =0.76,95%CI=0.51~1.15,P =0.20).Conclusion The IL-6-174C/G and-572C/G gene polymorphisms were suggested to be no related to the increased risk of hypertension in Asian.