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Exp Cell Res. 2016 Sep 10;347(1):95-104. doi: 10.1016/j.yexcr.2016.07.007. Epub 2016 Jul 15.

miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine.

Author information

1
Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China.
2
Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan, China.
3
Department of Medical Laboratory, Ningxia Medical University, Yinchuan, China.
4
Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
5
Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China; Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
6
Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China; Department of Basic Medicine, Ningxia Medical University, Yinchuan, China. Electronic address: jyjcyxy@yeah.net.

Abstract

MicroRNAs (miRNAs) are short non-coding RNA and play crucial roles in a wide array of biological processes, including cell proliferation, differentiation and apoptosis. Our previous studies found that homocysteine(Hcy) can stimulate the proliferation of vascular smooth muscle cells (VSMCs), however, the underlying mechanisms were not fully elucidated. Here, we found proliferation of VSMCs induced by Hcy was of correspondence to the miR-125b expression reduced both in vitro and in the ApoE knockout mice, the hypermethylation of p53, its decreased expression, and DNA (cytosine-5)-methyltransferase 3b (DNMT3b) up-regulated. And, we found DNMT3b is a target of miR-125b, which was verified by the Dual-Luciferase reporter assay and western blotting. Besides, the siRNA interference for DNMT3b significantly decreased the methylation level of p53, which unveiled the causative role of DNMT3b in p53 hypermethylation. miR-125b transfection further confirmed its regulative roles on p53 gene methylation status and the VSMCs proliferation. Our data suggested that a miR-125b-DNMT3b-p53 signal pathway may exist in the VSMCs proliferation induced by Hcy.

KEYWORDS:

Atherosclerosis; DNMT3b; Homocysteine; Vascular smooth muscle cells; miR-125b; p53

PMID:
27426728
DOI:
10.1016/j.yexcr.2016.07.007
[Indexed for MEDLINE]

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