title: A natural antisense transcript regulates acetylcholinesterase gene expression via epigenetic modification in Hepatocellular Carcinoma.
abstract: In recent years, widespread antisense transcripts have been identified systematically in mammalian cells and are known to regulate gene expression, although their functional significance remains largely unknown. Previous work has identified that acetylcholinesterase (AChE) is expressed aberrantly in various malignant tumors and function as a tumor growth suppressor. However, the mechanism of AChE gene regulation in tumors remains unclear. In this study, we show that the AChE antisense RNA (AChE-AS) play an important role in AChE expression regulation. An inverse relationship was identified between AChE-AS and AChE expression in hepatocellular carcinoma and hepatoma cells. The silenced AChE-AS corresponds to elevated expression of AChE. Furthermore, we demonstrated that reduced AChE-AS increased H3K4 methylation and decreased H3K9 methylation in the AChE promoter region. As expected, elevated AChE levels induced by inhibition of AChE-AS enhanced anticarcinogen-induced apoptosis. These observations demonstrated that AChE-AS modulates AChE expression and exerts an anti-apoptotic effect through direct repression of AChE expression in HCC cells. Thus, natural antisense RNA may play an important role in AChE regulation via affecting the epigenetic modification in the AChE promoter region.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China. Electronic address: xjzhang@sibcb.ac.cn.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D016685:Mitomycin / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D016372:RNA, Antisense; D016685:Mitomycin; D011065:Poly(ADP-ribose) Polymerases; D000110:Acetylcholinesterase; D008239:Lysine; D002945:Cisplatin
keywords: AChE antisense RNA; Acetylcholinesterase; Apoptosis; Cis-platin; Epigenetic modulation; Mitomycin C