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MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein

查看全文 作　　者：Min [1]Li;Qi [2]Wang;Shun-Ai [2]Liu;Jin-Qian [2]Zhang;Wei [2]Ju;Min [2]Quan;Sheng-Hu [1]Feng;Jin-Ling [1]Dong;Ping [2]Gao;Jun [1,2]Cheng 高影响力作者 机构地区：[1]Beijing Ditan Hospital, Teaching Hospital of Peking University;[2]Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University高影响力机构 出　　处：《World Journal of Gastroenterology》索引2015年第21卷第15期,共9页高影响力期刊 基　　金：Supported by Medical Specialty Development Projects of Beijing Municipal Administration of Hospitals,No.ZYLX201402;Ministry of Education of The People’s Republic of China,No.20121107110012;Beijing Municipal Commission of Education,No.11320016;Collaborative Innovation Center of Infectious Diseases and Beijing Key Laboratory of Emerging Infectious Diseases,Beijing,China 摘　　要：AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein. 关 键 词：CHOLESTEROL HEPATITIS C VIRUS core protein miR-185-5p STEATOSIS STEROL response ELEMENT bindingproteins
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