MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.

<h4>Background</h4>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 th...

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Autores principales:	Yung-Song Wang, Wen-Wen Chou, Ku-Chung Chen, Hsin-Yun Cheng, Ruey-Tay Lin, Suh-Hang Hank Juo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ae2aa9a21a84628876f07b4f3e560ad
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spelling	oai:doaj.org-article:2ae2aa9a21a84628876f07b4f3e560ad2021-11-18T07:29:20ZMicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.1932-620310.1371/journal.pone.0030635https://doaj.org/article/2ae2aa9a21a84628876f07b4f3e560ad2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22295098/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Yung-Song WangWen-Wen ChouKu-Chung ChenHsin-Yun ChengRuey-Tay LinSuh-Hang Hank JuoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e30635 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yung-Song Wang Wen-Wen Chou Ku-Chung Chen Hsin-Yun Cheng Ruey-Tay Lin Suh-Hang Hank Juo MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Yung-Song Wang Wen-Wen Chou Ku-Chung Chen Hsin-Yun Cheng Ruey-Tay Lin Suh-Hang Hank Juo
author_facet	Yung-Song Wang Wen-Wen Chou Ku-Chung Chen Hsin-Yun Cheng Ruey-Tay Lin Suh-Hang Hank Juo
author_sort	Yung-Song Wang
title	MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.
title_short	MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.
title_full	MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.
title_fullStr	MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.
title_full_unstemmed	MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.
title_sort	microrna-152 mediates dnmt1-regulated dna methylation in the estrogen receptor α gene.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2ae2aa9a21a84628876f07b4f3e560ad
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MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor α gene.

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