miR-503 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting the insulin receptor.
Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) is a common feature of disease progression in atherosclerosis. Here, we investigated the potential role of miR-503 in platelet-derived growth factor (PDGF)-induced proliferation and migration of human aortic smooth muscle cells and the underlying mechanisms of action. miR-503 expression was significantly downregulated in a dose- and time-dependent manner following PDGF treatment. Introduction of miR-503 mimics into cultured SMCs significantly attenuated cell proliferation and migration induced by PDGF. Bioinformatics analyses revealed that the insulin receptor (INSR) is a target candidate of miR-503. miR-503 suppressed luciferase activity driven by a vector containing the 3'-untranslated region of INSR in a sequence-specific manner. Downregulation of INSR appeared critical for miR-503-mediated inhibitory effects on PDGF-induced cell proliferation and migration in human aortic SMCs. Based on the collective data, we suggest a novel role of miR-503 as a regulator of VSMC proliferation and migration through modulating INSR.
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
Rui
R
Bi
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
Fangbao
F
Ding
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
Yi
Y
He
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
Lianyong
L
Jiang
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.
Zhaolei
Z
Jiang
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China. Electronic address: ju_mei63@126.com.
Ju
J
Mei
Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China. Electronic address: liuhao1619@gmail.com.
Hao
H
Liu
D020413:3' Untranslated Regions; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077214:Becaplermin; D001665:Binding Sites; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
D020413:3' Untranslated Regions; D015703:Antigens, CD; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C435941:INSR protein, human; D011972:Receptor, Insulin
INSR; Migration; Proliferation; VSMCs; miR-503