Activation of the oncogenic miR‐21‐5p promotes HCV replication and steatosis induced by the viral core 3a protein

• DOI: 10.1111/liv.14112
• Publication Date: 2019-04-02T13:52:27Z
• Authors: Sophie Clément; Cyril Sobolewski; Diana Gomes; Angela Rojas; Nicolas Goossens; Stéphanie Conzelmann; Nicolas Calo; Francesco Negro; Michelangelo Foti
• Keywords: Steatosis; Tensin

miR-21-5p is a potent oncogenic microRNA targeting many key tumour suppressors including phosphatase and tensin homolog (PTEN). We recently identified PTEN as factor modulated by hepatitis C virus (HCV) to promote virion egress. In hepatocytes, expression of HCV-3a core protein was sufficient downregulate trigger lipid droplet accumulation. Here, we investigated whether HCV controls through miR-21-5p-dependent mechanisms steatosis in hepatocytes life cycle.MiR-21-5p HCV-infected patients evaluated transcriptome meta-analysis. replication viral particle production were Jc1-infected Huh-7 cells after inhibition. assessed protein-expressing mouse primary having inhibited or genetically deleted respectively. core-induced vivo Mir21a knockout mice.MiR-21-5p significantly increased hepatic tissues from patients. Infection HCV-Jc1, transduction with core, upregulated and/or activity cells. inhibition decreased release infectious virions downregulation further prevented following hepatocytes. Finally, induction AAV8-mediated reduced activation molecular step, promoting both cycle may be among the changes induced carcinogenesis.