title: Aberrant hypermethylation of miR-9 genes in gastric cancer.
abstract: Carcinogenesis of the stomach involves multiple steps including genetic mutation or epigenetic alteration of tumor suppressor genes or oncogenes. Recently, tumor suppressive miRNAs have been shown to be deregulated by aberrant hypermethylation during gastric cancer progression. In this study, we demonstrate that three independent genetic loci encoding for miR-9 (miR-9-1, miR-9-2 and miR-9-3) are simultaneously modified by DNA methylation in gastric cancer cells. Methylation-mediated silencing of these three miR-9 genes can be reactivated in gastric cancer cells through 5-Aza-dC treatment. Subsequent analysis of the expression levels of miR-9 showed that it was significantly down-regulated in gastric cancers compared with adjacent normal tissues (P value < 0.005). A similar tendency toward a tumor-specific DNA methylation pattern was shown for miR-9-1, miR-9-2 and miR-9-3 in 72 primary human gastric cancer specimens. Ectopic expression of miR-9 inhibited cell proliferation, migration and invasion, suggesting its tumor suppressive potential in gastric cancer progression.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, China.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Liao
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: Wen-Ching
authors.initials: WC
authors.lastname: Chan
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Ho
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-chang
authors.initials: WC
authors.lastname: Lin
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs