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Title: Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway

Abstract

Highlights: ► MicroRNA-221 is upregulated in the endothelial progenitor cells of atherosclerosis patients. ► PAK1 is a direct target of microRNA-221. ► MicroRNA-221 inhibits EPCs proliferation through 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:
;  [1];  [2];  [3]; ;  [1];  [1]
  1. Department of Nuclear Medicine, Shanghai 10th People’s Hospital, Tongji University School of Medicine, Shanghai 200072 (China)
  2. Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001 (China)
  3. Department of Anatomy and neurobiology, School of Medicine, Tongji University, Shanghai 200072 (China)
Publication Date:
OSTI Identifier:
22239491
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 431; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARTERIOSCLEROSIS; CORONARIES; ENDOTHELIUM; INJURIES; LUCIFERASE; MORTALITY; PATIENTS

Citation Formats

Zhang, Xiaoping, Mao, Haian, Chen, Jin-yuan, Wen, Shengjun, Li, Dan, Ye, Meng, and Lv, Zhongwei. Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2012.12.157.
Zhang, Xiaoping, Mao, Haian, Chen, Jin-yuan, Wen, Shengjun, Li, Dan, Ye, Meng, & Lv, Zhongwei. Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway. United States. https://doi.org/10.1016/J.BBRC.2012.12.157
Zhang, Xiaoping, Mao, Haian, Chen, Jin-yuan, Wen, Shengjun, Li, Dan, Ye, Meng, and Lv, Zhongwei. 2013. "Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway". United States. https://doi.org/10.1016/J.BBRC.2012.12.157.
@article{osti_22239491,
title = {Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway},
author = {Zhang, Xiaoping and Mao, Haian and Chen, Jin-yuan and Wen, Shengjun and Li, Dan and Ye, Meng and Lv, Zhongwei},
abstractNote = {Highlights: ► MicroRNA-221 is upregulated in the endothelial progenitor cells of atherosclerosis patients. ► PAK1 is a direct target of microRNA-221. ► MicroRNA-221 inhibits EPCs proliferation through 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.},
doi = {10.1016/J.BBRC.2012.12.157},
url = {https://www.osti.gov/biblio/22239491}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 431,
place = {United States},
year = {Fri Feb 15 00:00:00 EST 2013},
month = {Fri Feb 15 00:00:00 EST 2013}
}