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

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• 作者：ChengJian Cao^a ; ¹ ; HuiPing Zhang^b ; ¹ ; Li Zhao^c ; Longxia Zhou^d ; Minghao Zhang^a ; ^d ; Hua Xu^a ; ^d ; Xuebo Han^c ; Guizhong Li^a ; ^d ; Xiaoling Yang^a ; ^d ; YiDeng Jiang^a ; ^d ; ^{jyjcyxy@yeah.net" class="auth_mail" title="E-mail the corresponding author}
• 关键词：VSMCs ; Vascular Smooth Muscle Cells ; AS ; atherosclerosis ; Hcy ; homocysteine ; HHcy ; Hyperhomocysteinemia ; DNMT3b ; DNA (cytosine-5)-methyltransferase 3b ; nMS-PCR ; nested methylation-specific-PCR ; UTR ; untranslated region ; miRNAs ; microRNAs ; mfe ; minimum free energy
• 刊名：Experimental Cell Research
• 出版年：2016
• 出版时间：10 September 2016
• 年：2016
• 卷：347
• 期：1
• 页码：95-104
• 全文大小：1490 K

文摘

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.