title: MiR-221 accentuates IFN׳s anti-HCV effect by downregulating SOCS1 and SOCS3.
abstract: MiR-221 was reported to be upregulated and play roles in tumorigenesis of hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC). However, the role of miR-221 in HCV infection remains unknown. In this study, it was found that miR-221 was upregulated in serum of HCV chronic hepatitis patients and Huh7.5.1 cells infected with HCVcc. Further studies indicated that miR-221 mimic could accentuate anti-HCV effect of IFN-α in HCVcc model, miR-221 mimic could further repressed 10% HCV RNA expression and 35-42% HCV core or NS5A protein expression in HCVcc infected Huh7.5.1 cells treated with 100IU/mL IFN-α, and miR-221 inhibitor resulted in the reverse effects. Furthermore, two members of suppressor of cytokine signaling (SOCS) family, SOCS1 and SOCS3, which are well established inhibitory factors on IFN/JAK/STAT pathway, were identified as the targets of miR-221 and were involved in the effect of miR-221. In conclusion, miR-221 could accentuate IFN׳s anti-HCV effect by targeting SOCS1 and SOCS3.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Fuzhou General Hospital of Nanjing Military Area Command, Fuzhou 350025, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China. Electronic address: wonwin29@126.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China. Electronic address: hmren@yahoo.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*
chemical_list: D016898:Interferon-alpha; D035683:MicroRNAs; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C525709:MIR221, human; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human
keywords: HCV; IFN-α; Mir-221; SOCS1; SOCS3