Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction.
Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction.
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作者：
Liu C;Yao MD;Li CP;Shan K;Yang H;Wang JJ;Liu B;Li XM;Yao J;Jiang Q;Yan B
血管功能障碍是缺血性、癌症和炎性疾病的标志，有助于疾病进展。环状RNA（CircRNA）是一种内源性非编码RNA，在多种人类疾病中表达异常。在这项研究中，我们使用视网膜血管来确定环状RNA在血管功能障碍中的作用。我们发现，cZNF 609在体内和体外高糖和缺氧应激时显著上调。cZNF 609沉默减少视网膜血管损失并抑制体内病理性血管生成。cZNF609基因沉默可促进内皮细胞迁移和管腔形成，保护内皮细胞免受氧化应激和缺氧应激的损伤。相反，转基因过表达cZNF 609表现出相反的效果。cZNF 609作为内源性miR-615 - 5p海绵，隔离并抑制miR-615 - 5p活性，导致MEF2A表达增加。MEF2A过表达可以挽救cZNF609沉默介导的对内皮细胞迁移、管形成和凋亡的影响。此外，在糖尿病、高血压和冠状动脉疾病患者的临床样本中检测到cZNF 609表达失调。cZNF 609表达的干预是治疗血管功能障碍的有希望的治疗方法。
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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影响因子：
1.5
作者：
Qazi, Yureeda;Maddula, Surekha;Ambati, Balamurali K.
通讯作者：
Ambati, Balamurali K.
影响因子：
4.5
作者：
Salzman J;Chen RE;Olsen MN;Wang PL;Brown PO
通讯作者：
Brown PO
影响因子：
9.5
作者：
Militello, Giuseppe;Weirick, Tyler;Uchida, Shizuka
通讯作者：
Uchida, Shizuka
影响因子：
16
作者：
Rybak-Wolf, Agnieszka;Stottmeister, Christin;Rajewsky, Nikolaus
通讯作者：
Rajewsky, Nikolaus
DOI：
10.1073/pnas.1604757113
发表时间：
2016-08-30
影响因子：
11.1
作者：
Puro, Donald G.;Kohmoto, Ryohsuke;Padovani-Claudio, Dolly A.
通讯作者：
Padovani-Claudio, Dolly A.