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

利用基因芯片技术对丙型肝炎病毒(HCV)感染的人肝脏中受调控的microRNAs进行鉴定。在人肝组织中，miR-422a表达下调，miR-199a-5p/199a-3p和miR-221/222表达上调，且呈纤维化进展相关。用实时荧光定量RT-PCR检测其表达情况。在这些miRNAs中，miR-222在两种纤维化模型的小鼠肝脏中增加。在培养的星状细胞LX-2中，miR-222的表达上调，并且在小鼠原代星状细胞依赖培养激活的过程中表达增加。NF-κB抑制剂可显著抑制α或α对培养细胞的诱导作用。虽然miR-222的过度表达或下调不能调节LX-2细胞的生长，但miR-222可与p27^&lt；Kip1&gt；3‘非编码区结合并调节相应蛋白的表达。瞬时转染组α-1(I)胶原蛋白表达明显上调，MMP1mRNA表达明显下调。结论：miR-222可能是星状细胞活化和肝纤维化进展的新标记物。

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.