title: Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs that play fundamental roles in diverse biological and pathological processes by targeting the expression of specific genes. Here, we identified 38 methylation-associated miRNAs, the expression of which could be epigenetically restored by cotreatment with 5-aza-2'-deoxycytidine and trichostatin A. Among these 38 miRNAs, we further analyzed miR-34b, miR-127-3p, miR-129-3p and miR-409 because CpG islands are predicted adjacent to them. The methylation-silenced expression of these miRNAs could be reactivated in gastric cancer cells by treatment with demethylating drugs in a time-dependent manner. Analysis of the methylation status of these miRNAs showed that the upstream CpG-rich regions of mir-34b and mir-129-2 are frequently methylated in gastric cancer tissues compared to adjacent normal tissues, and their methylation status correlated inversely with their expression patterns. The expression of miR-34b and miR-129-3p was downregulated by DNA hypermethylation in primary gastric cancers, and the low expression was associated with poor clinicopathological features. In summary, our study shows that tumor-specific methylation silences miR-34b and miR-129 in gastric cancer cells.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.forename: Ling-Yueh
authors.initials: LY
authors.lastname: Hu
authors.forename: Sung-Chou
authors.initials: SC
authors.lastname: Li
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Liao
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: Kuo-Hung
authors.initials: KH
authors.lastname: Huang
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Chan
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Lin
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D000077209:Decitabine; D015536:Down-Regulation; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D012334:RNA, Neoplasm; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine