Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells

被引：150

作者：

Saito, Y. ^{[1
]}

Suzuki, H. ^{[1
]}

Tsugawa, H. ^{[1
]}

Nakagawa, I. ^{[1
]}

Matsuzaki, J. ^{[1
]}

Kanai, Y. ^{[2
]}

Hibi, T. ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Shinjuku Ku, Tokyo 1608582, Japan

[2] Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 104, Japan

来源：

ONCOGENE | 2009年 / 28卷 / 30期

基金：

日本学术振兴会;

关键词：

miRNA; DNA methylation; histone modification; epigenetic treatment; Alu repeats; gastric cancer; MESSENGER-RNA; METHYLATION; THERAPY; TARGET; FUTURE;

D O I：

10.1038/onc.2009.140

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2'-deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer. Oncogene (2009) 28, 2738-2744; doi:10.1038/onc.2009.140; published online 8 June 2009

引用

页码：2738 / 2744

页数：7

共 26 条

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