Intrahepatic microRNA expression and response to peginterferon-α and ribavirin therapy in patients with chronic hepatitis C

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The regulated microRNAs(miRNAs) in human livers infected with hepatitis C virus(HCV) were identified by microarray analysis. MiR-422a was down-regulated, and miR-199a-5p/199a-3p and miR-221/222 up-regulated in the human liver in a fibrosis progression-dependent manner. Their expression was validated by real-time RT-PCR. Among these miRNAs, miR-222 increased in mouse livers from two fibrosis models. The expression of miR-222 was up-regulated in cultured stellate cells LX-2 and increased during the course of culture-dependent activation of mouse primary stellate cells. NF-κB inhibitor significantly suppressed the miR-222 induction that was stimulated in culture by TNF-α or TGF-α. Although over-expression or down-regulation of miR-222 failed to regulate the growth of LX-2 cells, miR-222 bound to the p27^<Kip1> 3'UTR and regulated the expression of the corresponding protein. Transient transfection with miR-222 precursors significantly up-regulated α1(I) collagen and down-regulated MMP-1 mRNA expressions. In conclusion, miR-222 may be new markers for stellate cell activation and liver fibrosis progression.