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.affiliation: Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China.
authors.forename: ChengJian
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: HuiPing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medical Laboratory, Ningxia Medical University, Yinchuan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
authors.forename: Longxia
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China; Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China; Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Medical Laboratory, Ningxia Medical University, Yinchuan, China.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China; Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
authors.forename: Guizhong
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Basic Research in Cardio-Cerebral Vascular Diseases, Ningxia Medical University, Yinchuan, China; Department of Basic Medicine, Ningxia Medical University, Yinchuan, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: YiDeng
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006710:Homocysteine / Q000494:pharmacology*; D008297:Male; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D006710:Homocysteine; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D000097584:DNA Methyltransferase 3B; C527468:Mirn125 microRNA, mouse
keywords: Atherosclerosis; DNMT3b; Homocysteine; Vascular smooth muscle cells; miR-125b; p53