title: Inhibition of microRNA-199a-5p reduces the replication of HCV via regulating the pro-survival pathway.
abstract: MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that post-transcriptionally regulate the pathological processes of various liver diseases including hepatitis C virus (HCV) infection. In the present study, we demonstrated that HCV infection enhanced the expression of miR-199a-5p in HCV infected human hepatocytes and Huh7.5.1cells, as well as liver biopsy specimens. Inhibition of miR-199a-5p decreased HCV replication not only in terms of HCV RNA, but also the protein levels of NS3 and NS5A. Furthermore, we discovered that miR-199a-5p knockdown in Huh7.5.1 cells infected with genotype 2a (JFH1) or genotype 1b (SN1a) resulted in the remarkable inhibition of pro-survival pathways, as observed by the down-regulation of p-Akt, p-ERK and β-catenin protein levels. Moreover, pre-treatment with the pro-survival pathway specific activator prominently ablated the inhibition of HCV replication induced by miR-199a-5p knockdown. Collectively, our results highlight the up-regulation of miR-199a-5p expression with HCV infection and the promotion of HCV replication by miR-199a-5p. Moreover, miR-199a-5p may facilitate HCV replication by regulating pro-survival pathways through PI3K/Akt, Ras/ERK and Wnt/β-catenin. miR-199a-5p might be a potential drug target for developing a novel strategy to combat HCV infection.
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
authors.forename: Shupeng
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China. Electronic address: xinwensongxx@163.com.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Song
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; C531408:mirn199 microRNA, human
keywords: HCV replication; Overexpression; Pro-survival pathway; miR-199a-5p