MiR-518a-5p Targets GZMB to Extenuate Vascular Endothelial Cell Injury Induced by Hypoxia-Reoxygenation and Thereby Improves Myocardial Ischemia

被引:8
作者
Yang, Hui [1 ]
Su, Jingjing [1 ]
Meng, Weixin [1 ]
Chen, Xiaoya [2 ]
Xu, Ying [3 ]
Sun, Bo [1 ]
机构
[1] Harbin Med Univ, Dept Cardiovasc Surg, Affiliated Hosp 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Dept Ultrasound, Affiliated Hosp 1, Harbin, Peoples R China
[3] Harbin Med Univ, Editorial Dept, Harbin, Peoples R China
关键词
H/R model; Dual-luciferase reporter gene assay; Proliferation; Apoptosis; GRANZYME-B; CARDIOMYOCYTE APOPTOSIS; MICRORNAS;
D O I
10.1536/ihj.20-619
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To probe the function of miR-518a-5p/Coanzyme B (GZMB) in hypoxia/reoxygenation (H/R)-induced vascular endothelial cell injury. The key genes of myocardial infarction were screened by bioinformatic methods. The upstream micro RNAs (miRNAs) of GZMB were predicted by TargetScan. The binding of miR-518a-5p to GZMB was verified with luciferase reporter assay. The H/R model was constructed with human vascular endothelial cell (HUVEC) in vitro. Cell Counting Kit-8 (CCK8) assay was performed to detect cell proliferation. Western blot was utilized to evaluate the levels of indicated proteins. GZMB was up-regulated in patients with myocardial infarction and identified as the key gene by the bioinformatics analysis. Then the prediction from Target-Scan indicated that miR-518a-5p, which is down-regulated in myocardial infarction patients. might be the potential upstream miRNA for GZMB. The following experiments verified that miR-518a-5p could bind to the 3'UTR of GZMB and negatively modulates GZMB expression. More importantly, the miR-518a-5p mimic enhanced cell proliferation and repressed apoptosis of H/R-injured HUVEC cells by inhibiting GZMB expression. We proved that miR-518a-5p could partly attenuate H/R-induced HUVEC cell injury by targeting GZMB, and perhaps the miR-518a-5p/GZMB axis could be potential therapeutic targets for myocardial infarction.
引用
收藏
页码:658 / 665
页数:8
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