A regulatory circuit involving miR-143 and DNMT3a mediates vascular smooth muscle cell proliferation induced by homocysteine.
Mol Med Rep
; 13(1): 483-90, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26573388
ABSTRACT
Accumulating evidence has suggested that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS). Hcy can promote vascular smooth muscle cell (VSMC) proliferation, which is pivotal in the pathogenesis and progression of AS. The aim of the present study was to investigate the epigenetic regulatory mechanism of microRNA (miR)143mediated VSMCs proliferation induced by Hcy. The results of a 3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide assay revealed that VSMC proliferation was increased by 1.39fold following treatment with 100 mM Hcy, compared with the control group. The levels of miR143 were markedly downregulated in the Hcy group, compared with the control group, as determined using reverse transcriptionquantitative polymerase chain reaction analysis. In addition, the level of miR143 methylation was increased markedly in the VSMCs treated with Hcy, compared with the control, and was reduced following transfection with DNA methyltransferase (DNMT)3a small interfering RNA, determined using methylationspecificPCR. The activities of DNMT3a luciferase were also altered accordingly in VSMCs transfected with premiR143 and miR143 inhibitor, respectively. In addition, the expression of miR143 was observed to be inversely correlated with the mRNA and protein expression of DNMT3 in the VSMCs. Taken together, these findings suggest that DNMT3a is a direct target of miR143, and that the upregulation of DNMT3 is responsible for the hypermethylation of miR143 in Hcy-induced VSMC proliferation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Miócitos de Músculo Liso
/
MicroRNAs
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DNA (Citosina-5-)-Metiltransferases
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Redes Reguladoras de Genes
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Homocisteína
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Músculo Liso Vascular
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article