title: EVI1 promotes cell proliferation in HBx-induced hepatocarcinogenesis as a critical transcription factor regulating lncRNAs.
abstract: The involvement of the hepatitis B virus X (HBx) protein in epigenetic modifications during hepatocarcinogenesis has been previously characterized. Long noncoding RNAs (lncRNAs), a kind of epigenetic regulator molecules, have also been shown to play crucial roles in HBx-related hepatocellular carcinoma (HCC). In this study, we analyzed the key transcription factors of aberrantly expressed lncRNAs in the livers of HBx transgenic mice by bioinformatics prediction, and found that ecotropic viral integration site 1 (Evi1) was a potential main transcription regulator. Further investigation showed that EVI1 was positively correlated to HBx expression and was frequently up-regulated in HBV-related HCC tissues. The forced expression of HBx in liver cell lines resulted in a significant increase of the expression of EVI1. Furthermore, suppression of EVI1 expression decreased the proliferation of HCC cells overexpressing HBx in vitro and in vivo.
  
  
  CONCLUSIONS
  Our findings suggest that EVI1 is frequently up-regulated and regulates a cluster of lncRNAs in HBV-related hepatocellular carcinoma (HCC). These findings highlight a novel mechanism for HBx-induced hepatocarcinogenesis through transcription factor EVI1 and its target lncRNAs, and provide a potential new approach to predict the functions of lncRNAs.
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Huang
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Chen-Xi
authors.initials: CX
authors.lastname: Zhao
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Guo
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology*; D049109:Cell Proliferation / Q000235:genetics; D002472:Cell Transformation, Viral / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology*; D000074008:MDS1 and EVI1 Complex Locus Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; D062085:RNA, Long Noncoding
keywords: ecotropic viral integration site 1; hepatitis B virus X protein; hepatocellular carcinoma; long non-coding RNA; transcription factor