PMID- 28472596 OWN - NLM STAT- MEDLINE DCOM- 20170908 LR - 20220311 IS - 1557-7430 (Electronic) IS - 1044-5498 (Linking) VI - 36 IP - 6 DP - 2017 Jun TI - Reciprocal Regulation Between miR-148a/152 and DNA Methyltransferase 1 Is Associated with Hyperhomocysteinemia-Accelerated Atherosclerosis. PG - 462-474 LID - 10.1089/dna.2017.3651 [doi] AB - DNA methyltransferase 1 (DNMT1) and miRNAs are both important regulators of gene expression that have been implicated in the pathogenesis of atherosclerosis. This study was designed to elucidate the potential interaction between DNMT1 and miRNAs in the context of hyperhomocysteinemia (HHcy)-related atherosclerosis. In the aorta of ApoE(-/-) mice fed a high methionine diet, increased expression of miR-148a/152, with decreased DNMT1 mRNA and protein levels, was detected. Similar changes were observed in cultured foam cells stimulated with homocysteine. When miR-148a/152 was overexpressed using viral vectors, DNMT1 expression was suppressed, whereas the expression of adipose differentiation-related protein (ADRP) was enhanced, and the contents of total cholesterol (TC) and cholesteryl ester (CE) were increased in cultured foam cells. Conversely, downregulation of miR-148a/152 led to elevated DNMT1 expression, reduced ADRP expression, and lowered contents of TC and CE. The luciferase reporter assay verified that DNMT1 is a target gene for miR-148a/152 and overexpression of DNMT1 can partially reverse the miR-148a/152-induced lipid accumulation in foam cells. Meanwhile, we observed that DNMT1 overexpression enhanced DNA methylation and reduced miR-148a/152 expression. Our data showed reciprocal regulation between miR-148a/152 and DNMT1 in foam cells, which likely plays a critical role in HHcy-related atherosclerosis. FAU - Yang, Anning AU - Yang A AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Sun, Yue AU - Sun Y AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Gao, Yuan AU - Gao Y AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Yang, Songhao AU - Yang S AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Mao, Caiyan AU - Mao C AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Ding, Ning AU - Ding N AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Deng, Mei AU - Deng M AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Wang, Yanhua AU - Wang Y AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Yang, Xiaoling AU - Yang X AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Jia, Yuexia AU - Jia Y AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . FAU - Zhang, Huiping AU - Zhang H AD - 2 Prenatal Diagnosis Center of Ningxia Medical University General Hospital , Yinchuan, China . FAU - Jiang, Yideng AU - Jiang Y AD - 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University , Yinchuan, China . LA - eng PT - Journal Article DEP - 20170504 PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - 0 (Apolipoproteins E) RN - 0 (Cholesterol Esters) RN - 0 (MIRN152 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn148 microRNA, mouse) RN - 97C5T2UQ7J (Cholesterol) RN - AE28F7PNPL (Methionine) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (DNMT1 protein, human) RN - EC 2.1.1.37 (Dnmt1 protein, mouse) SB - IM MH - Animals MH - Apolipoproteins E/deficiency/genetics MH - Atherosclerosis/*complications/enzymology/*genetics/pathology MH - Cell Line, Tumor MH - Cholesterol/metabolism MH - Cholesterol Esters/metabolism MH - DNA (Cytosine-5-)-Methyltransferase 1 MH - DNA (Cytosine-5-)-Methyltransferases/*metabolism MH - DNA Methylation/drug effects MH - Foam Cells/drug effects/metabolism MH - Humans MH - Hyperhomocysteinemia/*complications MH - Methionine/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics MH - Promoter Regions, Genetic/genetics OTO - NOTNLM OT - DNA methylation OT - DNMT1 OT - atherosclerosis OT - homocysteine OT - miR-148a/152 EDAT- 2017/05/05 06:00 MHDA- 2017/09/09 06:00 CRDT- 2017/05/05 06:00 PHST- 2017/05/05 06:00 [pubmed] PHST- 2017/09/09 06:00 [medline] PHST- 2017/05/05 06:00 [entrez] AID - 10.1089/dna.2017.3651 [doi] PST - ppublish SO - DNA Cell Biol. 2017 Jun;36(6):462-474. doi: 10.1089/dna.2017.3651. Epub 2017 May 4.