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Epigenetic regulation of miR‐34b and miR‐129 expression in gastric cancer
Author(s) -
Tsai KuoWang,
Wu ChewWun,
Hu LingYueh,
Li SungChou,
Liao YuLun,
Lai ChunHung,
Kao HsiaoWei,
Fang WenLiang,
Huang KuoHung,
Chan WenChing,
Lin WenChang
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25919
Subject(s) - microrna , dna methylation , epigenetics , methylation , cpg site , demethylating agent , biology , cancer , cancer research , trichostatin a , gene silencing , regulation of gene expression , gene expression , gene , genetics , histone , histone deacetylase
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.