Microrna-152 mediates dnmt1-regulated dna methylation in the estrogen receptor α gene

Yung Song Wang, Wen Wen Chou, Ku Chung Chen, Hsin Yun Cheng, Ruey Tay Lin, Suh Hang Hank Juo

研究成果: 雜誌貢獻文章同行評審

63 引文 斯高帕斯(Scopus)

摘要

Background: Estrogen receptor α (ERα) has been shown to protect against atherosclerosis. Methylation of the ERα gene can reduce ERα expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs involved in DNMT-associated DNA methylation in the ERα gene. We also tested whether statin and a traditional Chinese medicine (San-Huang-Xie-Xin-Tang, SHXXT) could exert a therapeutic effect on microRNA, DNMT and ERα methylation. Methodology/Principal Findings: The ERα expression was decreased and ERα methylation was increased in LPS-treated human aortic smooth muscle cells (HASMCs) and the aorta from rats under a high-fat diet. microRNA-152 was found to be down regulated in the LPS-treated HASMCs. We validated that microRNA-152 can knock down DNMT1 in HASMCs leading to hypermethylation of the ERα gene. Statin had no effect on microRNA-152, DNMT1 or ERα expression. On the contrary, SHXXT could restore microRNA-152, decrease DNMT1 and increase ERα expression in both cellular and animal studies. Conclusions/Significance: The present study showed that microRNA-152 decreases under the pro-atherosclerotic conditions. The reduced microRNA-152 can lose an inhibitory effect on DNA methyltransferase, which leads to hypermethylation of the ERα gene and a decrease of ERα level. Although statin can not reverse these cascade proatherosclerotic changes, the SHXXT shows a promising effect to inhibit this unwanted signaling pathway.

原文英語
文章編號e30635
期刊PLoS One
7
發行號1
DOIs
出版狀態已發佈 - 一月 25 2012
對外發佈

ASJC Scopus subject areas

  • 農業與生物科學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 醫藥 (全部)

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