摘要：

Hepatitis C virus(HCV)infection induces chronic hepatic inflammation,which usually favors the initiation and progression of cancer.It is also increasing clearly that microRNA-155 (miR-155)plays an important role in regulating both inflammation and tumorigenesis.However,little is known about whether and how miR-155 provides the link between inflammation and cancer.Here we found that miR-155 levels were markedly increased after HCV infection and in hepatitis C.miR-155 expression was transcribed by NF-κB,and p300/CBP increased NF-κB-dependent miR-155 expression.Overexpression of miR-155 significantly inhibited hepatocytes apoptosis and promoted cells growth,whereas miR-155 inhibition induced G0/G1 arrest.Upregulated miR-155 resulted in nuclear accumulation of β-catenin and a concomitant increase in cyclin D1,c-myc and survivin.Gain-of-function and loss-of-function studies demonstrated that miR-155 promoted hepatocytes proliferation and tumorigenesis by increasing Wnt signaling in vitro and in vivo,and DKK1(Wnt pathway inhibitor)overexpression inhibited the biological role of miR-155 in hepatocytes.Finally,adenomatous polyposis coli(APC),which negatively regulates Wnt signaling,was identified as the direct and functional target of miR-155.Conclusion:Hepatitis C-induced upregulation of miR-155 promotes hepatocytes proliferation and tumorigenesis by activating Wnt signaling.The present study provides a better understanding of the relationship between inflammation and tumor,and thus may be helpful in developing effective diagnosis and treatment strategies against HCV-HCC.

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