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

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.

Authors:
 [1];  [2];  [3];  [4]; ;  [1];  [5];  [3]; ;  [1];  [5];  [1];  [5]
  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. (China)
Publication Date:
OSTI Identifier:
22649755
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 347; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; ARTERIOSCLEROSIS; CELL PROLIFERATION; CYTOSINE; DNA; FREE ENERGY; GENES; HOMOCYSTEINE; IN VITRO; KNOCK-OUT REACTIONS; LUCIFERASE; METHYL TRANSFERASES; METHYLATION; MICE; MUSCLES; POLYMERASE CHAIN REACTION; RNA

Citation Formats

Cao, ChengJian, Zhang, HuiPing, Zhao, Li, Zhou, Longxia, Zhang, Minghao, Xu, Hua, Department of Basic Medicine, Ningxia Medical University, Yinchuan, Han, Xuebo, Li, Guizhong, Yang, Xiaoling, Department of Basic Medicine, Ningxia Medical University, Yinchuan, Jiang, YiDeng, E-mail: jyjcyxy@yeah.net, and Department of Basic Medicine, Ningxia Medical University, Yinchuan. miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.07.007.
Cao, ChengJian, Zhang, HuiPing, Zhao, Li, Zhou, Longxia, Zhang, Minghao, Xu, Hua, Department of Basic Medicine, Ningxia Medical University, Yinchuan, Han, Xuebo, Li, Guizhong, Yang, Xiaoling, Department of Basic Medicine, Ningxia Medical University, Yinchuan, Jiang, YiDeng, E-mail: jyjcyxy@yeah.net, & Department of Basic Medicine, Ningxia Medical University, Yinchuan. miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine. United States. doi:10.1016/J.YEXCR.2016.07.007.
Cao, ChengJian, Zhang, HuiPing, Zhao, Li, Zhou, Longxia, Zhang, Minghao, Xu, Hua, Department of Basic Medicine, Ningxia Medical University, Yinchuan, Han, Xuebo, Li, Guizhong, Yang, Xiaoling, Department of Basic Medicine, Ningxia Medical University, Yinchuan, Jiang, YiDeng, E-mail: jyjcyxy@yeah.net, and Department of Basic Medicine, Ningxia Medical University, Yinchuan. Sat . "miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine". United States. doi:10.1016/J.YEXCR.2016.07.007.
@article{osti_22649755,
title = {miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine},
author = {Cao, ChengJian and Zhang, HuiPing and Zhao, Li and Zhou, Longxia and Zhang, Minghao and Xu, Hua and Department of Basic Medicine, Ningxia Medical University, Yinchuan and Han, Xuebo and Li, Guizhong and Yang, Xiaoling and Department of Basic Medicine, Ningxia Medical University, Yinchuan and Jiang, YiDeng, E-mail: jyjcyxy@yeah.net and Department of Basic Medicine, Ningxia Medical University, Yinchuan},
abstractNote = {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.},
doi = {10.1016/J.YEXCR.2016.07.007},
journal = {Experimental Cell Research},
number = 1,
volume = 347,
place = {United States},
year = {Sat Sep 10 00:00:00 EDT 2016},
month = {Sat Sep 10 00:00:00 EDT 2016}
}