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The role of long non-coding RNAs(lncRNAs)in tumorigenesis is gradually being elucidated largely due to an increasing number of studies.However,the regulatory mechanism for lncRNA expression remains unclear.In this study,we employed a systemic approach to analyze the key regulator of aberrantly expressed lncRNAs in HBV X protein(HBx)-transgenic mice,which is a well-proven mouse tumorigenesis model for hepatitis B virus-related hepatocellular carcinoma.With a bioinformatics analysis of microarray data,ecotropic viral integration site 1(Evi-1)was identified as a key regulatory transcriptional factor contributing to the aberrant expression of lncRNAs in the livers of HBx-transgenic mice.As a consequence of the up-regulation of Evi-1,we also identified that an Evi-1-regulated lncRNA AK015487 contributed to hepatocyte proliferative activity and apoptosis.Our findings highlight a novel mechanism for hepatocellular carcinoma tumorigenesis through Evi-1 and its target lncRNAs.In addition,our study also provides a good model for investigation of the regulatory mechanism for lncRNA expression using a systemic approach.