IARS2 regulates proliferation, migration, and angiogenesis of human umbilical vein endothelial cells

被引:1
|
作者
Yu, Yue-ming [1 ]
Xu, Liang [1 ]
Li, Hao-ran [1 ]
Zhang, Tie-qi [1 ]
Qian, Guang [1 ]
Li, Ling-feng [1 ]
Wang, Ming-hai [1 ]
机构
[1] Fudan Univ, Peoples Hosp Shanghai 5, Dept Orthoped, Shanghai, Peoples R China
来源
关键词
Human umbilical vein endothelial cells; Isoleucine-tRNA ligase; Angiogenic proteins; Cell proliferation; Cell migration; TRANSFER-RNA SYNTHETASES; TUMOR ANGIOGENESIS; CANCER CELLS; GROWTH; ASSOCIATION; KNOCKDOWN; GENE;
D O I
10.1590/1806-9282.20201024
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1- isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti- isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl- tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase 1/2 and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3 beta, and beta-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase 1/2 and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3 beta, and beta-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.
引用
收藏
页码:555 / 560
页数:6
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