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MicroRNA-513a-5p mediates TNF-α and LPS induced apoptosis via downregulation of X-linked inhibitor of apoptotic protein in endothelial cells

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Author(s)
Sojin ShinKyo Chul MoonKeon Uk ParkEunyoung Ha
Keimyung Author(s)
Shin, So JinMun, Kyo CheolHa, Eun YoungPark, Keon Uk
Department
Dept. of Obstetrics & Gynecology (산부인과학)
Dept. of Biochemistry (생화학)
Dept. of Internal Medicine (내과학)
Journal Title
Biochimie
Issued Date
2012
Volume
94
Issue
6
Abstract
MicroRNAs (miRNAs) are endogenous non-coding small RNAs that have emerged as one of the central players of gene expression regulation. Endothelial cell apoptosis plays a fundamental role in the development of atherosclerosis. This study was designed to determine the effect of miR-513a-5p on apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) and miR-513a-5p expression levels were determined. MiR-513a-5p target gene indentification, validation, and signalling pathways were investigated. Treatment of HUVECs with TNF-α and LPS up-regulated miR-513a-5p expressions more than 2-fold compared to control (P < 0.05). Inhibition of miR-513a-5p by antisense (AS) miR-513a-5p reversed TNF-α and LPS induced apoptosis (P < 0.01). Transfection of HUVECs with miR-513a-5p mimics also induced apoptosis (P < 0.01). Treatment of HUVECs with TNF-α and LPS attenuated X-linked inhibitor of apoptosis (XIAP) while increased caspase-3 expression, poly ADP-ribose polymerase (PARP) cleavage, and p53 expression. These effects were reversed by inhibition of miR-513a-5p. Of those miR-513a-5p candidate target genes, we identified and validated XIAP as a miR-513a-5p target gene. Targeting of the XIAP 3′-untranslated region by miR-513a-5p using luciferase reporter assay resulted in attenuated luciferase activity. Transfection of HUVECs with AS miR-513a-5p increased XIAP protein expression while miR-513a-5p mimics attenuated XIAP expression. These results together suggest that miR-513a-5p mediates TNF-α and LPS induced apoptosis via downregulation of XIAP in HUVECs.
Keimyung Author(s)(Kor)
신소진
문교철
하은영
박건욱
Publisher
School of Medicine
Citation
Sojin Shin et al. (2012). MicroRNA-513a-5p mediates TNF-α and LPS induced apoptosis via
downregulation of X-linked inhibitor of apoptotic protein in endothelial cells. Biochimie, 94(6), 1431–1436. doi: 10.1016/j.biochi.2012.03.023
Type
Article
ISSN
0300-9084
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0300908412001307?via%3Dihub
DOI
10.1016/j.biochi.2012.03.023
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33706
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
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