MiR-135b-5p and MiR-499a-3p Promote Cell Proliferation and Migration in Atherosclerosis by Directly Targeting MEF2C

• Published in: Scientific reports Vol. 5; no. 1; p. 12276
• Main Authors: Xu, Zhiliang, Han, Yeming, Liu, Jiying, Jiang, Fan, Hu, Huili, Wang, Yan, Liu, Qiji, Gong, Yaoqin, Li, Xi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2015; Nature Publishing Group
• Subjects: 13/1; 13/51; 14/34; 3' Untranslated Regions; 38/109; 38/61; 38/70; 38/77; 631/337/384/331; 631/80/304; 96/44; Adult; Arteriosclerosis; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Base Sequence; Binding Sites; Cardiovascular disease; Case-Control Studies; Cell growth; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cluster Analysis; Coronary artery; Coronary Artery Disease - genetics; Coronary Artery Disease - pathology; Endothelial cells; Endothelial Cells - metabolism; Female; Gene Expression Profiling; Gene Expression Regulation; Heart diseases; Human Umbilical Vein Endothelial Cells; Humanities and Social Sciences; Humans; Male; MEF2 Transcription Factors - genetics; MEF2 Transcription Factors - metabolism; MicroRNAs - genetics; Middle Aged; miRNA; multidisciplinary; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - metabolism; Plaque, Atherosclerotic; Reproducibility of Results; RNA Interference; RNA, Messenger - genetics; Science; Smooth muscle; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep12276

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.