【作者】 郭瀛军； 王越； 刘音； 黄金凤； 孙树汉；

【机构】 第二军医大学医学遗传学教研室；

【Abstract】 Background & Aims:The involvement of the hepatitis B virus X(HBx) protein in epigenetic modifications during hepatocarcinogenesis has been previously characterized.Long noncoding RNAs(IncRNAs),a kind of epigenetic regulator molecule have also been shown to have critical regulatory roles in cancer biology.However,the contributions of HBx protein to IncRNAs in hepatocellular carcinoma(HCC) remain largely unknown.Methods & Results:In this study,we analyze the key regulator of aberrantly expressed IncRNAs in HBx transgenic mice. Our results showed that the transcriptional regulator ecotropic viral integration site 1(Evi1) is a potential main regulator of differential expressed IncRNAs and mRNAs in HBx transgenic mouse liver.Evi1 was positively correlated to HBx messenger RNA(mRNA) expression and was frequently up-regulated in HBV-related HCC tissues in comparison with adjacent noncancerous hepatic tissues.The forced expression of HBx in liver cell lines resulted in a significant increase of the expression of Evi1 at both the the mRNA and protein levels,which in turn led to obvious expression change of Evi1 target genes GATA-2 and PTEN.Furthermore,suppression of Evi1 expression by small interfering RNA decreased the proliferation of HCC cells overexpressing HBx in vitro and vivo.As a consequence of the up-regulation of Evi1,we also identified mat Evi1-regulated lncRNA AK015487 and AK016494 contributed to hepatocyte proliferative activity. Conclusion:Our findings suggest that Evi1 is frequently up-regulated and regulates a culster of IncRNAs in HBV-related hepatocellular carcinoma(HCC).These findings highlight a novel mechanism for HBV-related hepatocellular carcinoma tumorigenesis through Evi1 and its target IncRNAs.更多还原