title: MiR-135b-5p and MiR-499a-3p Promote Cell Proliferation and Migration in Atherosclerosis by Directly Targeting MEF2C.
abstract: Proliferation and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are critical processes involved in atherosclerosis. Recent studies have revealed that microRNAs (miRNAs) can be detected in circulating blood with a stable form and the expression profiles differ in many cellular processes associated with coronary artery disease (CAD). However, little is known about their role, especially serum-derived miRNAs, in ECs and VSMCs phenotype modulation during atherosclerosis. We compared the miRNA expressions in serum samples from 13 atherosclerotic CAD patients and 5 healthy control subjects and identified 36 differentially expressed miRNAs. The expression of selected miRNAs (miR-135b-5p and miR-499a-3p) was further validated in 137 serum samples. Interestingly, miR-135b-5p and miR-499a-3p directly regulated a common target gene: myocyte enhancer factor 2C (MEF2C) which plays an important role in modulating cell phenotype of cardiovascular systems. Furthermore, our results indicated that the 2 elevated miRNAs could jointly promote ECs and VSMCs proliferation and migration by repressing MEF2C expression. Together, our findings demonstrated a serum-based miRNA expression profile for atherosclerotic CAD patients, potentially revealing a previously undocumented mechanism for cell proliferation and migration mediated by miR-135b-5p and miR-499a-3p, and might provide novel insights into the role of circulating miRNAs in atherosclerosis pathogenesis.
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education Institute of Medical Genetics, School of Medicine, Shandong University Jinan, Shandong 250012, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Yeming
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Interventional Treatment, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education and Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education Institute of Medical Genetics, School of Medicine, Shandong University Jinan, Shandong 250012, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Hu
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education Institute of Medical Genetics, School of Medicine, Shandong University Jinan, Shandong 250012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education Institute of Medical Genetics, School of Medicine, Shandong University Jinan, Shandong 250012, China.
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education Institute of Medical Genetics, School of Medicine, Shandong University Jinan, Shandong 250012, China.
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Key Laboratory of Experimental Teratology, Ministry of Education Institute of Medical Genetics, School of Medicine, Shandong University Jinan, Shandong 250012, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D016000:Cluster Analysis; D003324:Coronary Artery Disease / Q000235:genetics / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058226:Plaque, Atherosclerotic; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D064326:MEF2 Transcription Factors; C544965:MIRN135 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger