Aberrant microRNAs (miRNAs) expression plays a privotal role in the development of liver fibrosis.However,the functional role of miRNAs in Hepatitis C virus (HCV)-related fibrosis remains largely unknown.In this study,we systematically analyzed the serum miRNAs by microarray analysis in HCV-induced hepatic fibrosis.Thirty up-regulated miRNAs and 11 down-regulated miRNAs in the serum samples were identified.Among these dysregulated miRNAs,miR-1273g-3p was the most significant up-regulated miRNA,and its serum level was significantly correlated with liver fibrosis stages (Rho=0.577).Further,increased expression level of miR-1273g-3p was also present in activated hepatic stellate cells (HSCs).Knockdown of miR-1273g-3p by target inhibitor could blockade the expression of α-SMA,Col1A1 and induce apoptosis of HSCs.Luciferase reporter assay was performed to confirm PTEN as a direct target of miR-1273g-3p.Increased miR-1273g-3p expression of HSCs could reduce PTEN transcription by binding to the 3-untranslated regions of PTEN mRNA.Moreover,overexpression of PTEN could also suppress the expression of α-SMA,CollA1 and induce HSC apoptosis.Hence,we concluded that miR-1273g-3p promoted HCV-induced liver fibrogenesis by activating HSCs and inhibiting HSC apoptosis through suppressing PTEN and its downstream signaling pathway.These results provide novel mechanistic insights for the profibrotic effect of miR-1273g-3p.