title: Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway.
abstract: Coronary artery disease (CAD) is associated with high mortality and occurs via endothelial injury. Endothelial progenitor cells (EPCs) restore the integrity of the endothelium and protect it from atherosclerosis. In this study, we compared the expression of microRNAs (miRNAs) in EPCs in atherosclerosis patients and normal controls. We found that miR-221 expression was significantly up-regulated in patients compared with controls. We predicted and identified p21/Cdc42/Rac1-activated kinase 1 (PAK1) as a novel target of miR-221 in EPCs. We also demonstrated that miR-221 targeted a putative binding site in the 3'UTR of PAK1, and absence of this site was inversely associated with miR-221 expression in EPCs. We confirmed this relationship using a luciferase reporter assay. Furthermore, overexpression of miR-221 in EPCs significantly decreased EPC proliferation, in accordance with the inhibitory effects induced by decreased PAK1. Overall, these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation of EPCs.
authors: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
authors: Xiaoping
authors: X
authors: Zhang
authors: Haian
authors: H
authors: Mao
authors: Jin-yuan
authors: JY
authors: Chen
authors: Shengjun
authors: S
authors: Wen
authors: Dan
authors: D
authors: Li
authors: Meng
authors: M
authors: Ye
authors: Zhongwei
authors: Z
authors: Lv
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D013234:Stem Cells / Q000201:enzymology* / Q000473:pathology; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D019908:Proto-Oncogene Proteins c-raf; D054462:p21-Activated Kinases; C525709:MIR221, human; C515903:PAK1 protein, human