title: Epigenetic regulation of miR-196b expression in gastric cancer.
abstract: MicroRNAs (miRNAs) are short noncoding RNAs that play important roles in cellular processes and disease pathogenesis via the control of specific targeted gene expression. The miR-196s miRNA is encoded at three paralogous loci in three HOX clusters and acts as an oncogenic miRNA in cancer progression. Recent studies have demonstrated that the expression of miR-196b increases cell proliferation and survival in leukemic cells. Here, we used a sequential methylation analysis to reveal that the methylation status correlated well with miR-196b expression in different cell lines. Treatment with the demethylating drug 5-Aza-dC reactivated miR-196b transcription in methylation-silenced cells. Using in vitro methylation approach, we further provide evidences that promoter hypermethylation represses miR-196b transcriptional activation tightly in human cancer cell lines. We also demonstrate that the expression of miR-196b is significantly elevated in gastric cancer and that hypomethylation status of miR-196b CpG islands frequently is observed in primary gastric tumors. Our results provide important information on miR-196s regulation and demonstrate that abnormal DNA hypomethylation induces overexpression of miR-196b in gastric cancer.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
authors.forename: Ling-Yueh
authors.initials: LY
authors.lastname: Hu
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.forename: Sung-Chou
authors.initials: SC
authors.lastname: Li
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lai
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Kao
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Fang
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Lin
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D000077209:Decitabine; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D017931:DNA Primers; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D000077209:Decitabine; D001374:Azacitidine