基因沉默
血管生成
内皮干细胞
生物
癌症研究
体内
内皮功能障碍
细胞生物学
氧化应激
小干扰RNA
环状RNA
病理
核糖核酸
体外
医学
内分泌学
基因
生物化学
生物技术
作者
Chang Liu,Mu-Di Yao,Chaopeng Li,Kun Shan,Hong Yang,Jintao Wang,Ban Liu,Xiu-Miao Li,Jin Yao,Qin Jiang,Biao Yan
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2017-07-08
卷期号:7 (11): 2863-2877
被引量:184
摘要
Vascular dysfunction is a hallmark of ischemic, cancer, and inflammatory diseases, contributing to disease progression. Circular RNAs (circRNAs) are endogenous non-coding RNAs, which have been reported to be abnormally expressed in many human diseases. In this study, we used retinal vasculature to determine the role of circular RNA in vascular dysfunction. We revealed that cZNF609 was significantly up-regulated upon high glucose and hypoxia stress in vivo and in vitro. cZNF609 silencing decreased retinal vessel loss and suppressed pathological angiogenesis in vivo. cZNF609 silencing increased endothelial cell migration and tube formation, and protected endothelial cell against oxidative stress and hypoxia stress in vitro. By contrast, transgenic overexpression of cZNF609 showed an opposite effects. cZNF609 acted as an endogenous miR-615-5p sponge to sequester and inhibit miR-615-5p activity, which led to increased MEF2A expression. MEF2A overexpression could rescue cZNF609 silencing-mediated effects on endothelial cell migration, tube formation, and apoptosis. Moreover, dysregulated cZNF609 expression was detected in the clinical samples of the patients with diabetes, hypertension, and coronary artery disease. Intervention of cZNF609 expression is promising therapy for vascular dysfunction.
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