title: MiR-21 inhibits c-Ski signaling to promote the proliferation of rat vascular smooth muscle cells.
abstract: Previously, we reported that the decrease of endogenous c-Ski expression is implicated in the progression of vascular smooth muscle cell (VSMC) proliferation after arterial injury. However, the molecular mechanism of the down-regulation of c-Ski is not clear. In this study, a potential miR-21 recognition element was identified in the 3'-untranslated region (UTR) of rat c-Ski mRNA. A reporter assay revealed that miR-21 could recognize the miR-21 recognition element of c-Ski mRNA. In A10 rat aortic smooth muscle cells, overexpression of miR-21 significantly inhibited the expression of c-Ski protein and promoted cell proliferation, which could be blocked by inhibition of miR-21 or overexpression of c-Ski. Further investigation demonstrated that the effect of miR-21 on VSMC proliferation resulted from negative regulation of c-Ski to suppress p38-p21/p27 signaling, the downstream pathway of c-Ski in VSMCs. These results indicate that c-Ski is a target gene of miR-21. miR-21 specifically binds to the 3'-untranslated region of c-Ski and negatively regulates c-Ski expression to diminish the protective effects of c-Ski and stimulate VSMC proliferation in the progression of arterial injury.
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: tmmubiodss@aliyun.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xie
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000293:injuries; D049109:Cell Proliferation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C525545:Ski protein, rat; C546082:mirn21 microRNA, rat; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Proliferation; VSMC; c-Ski; miR-21