MicroRNA-939 governs vascular integrity and angiogenesis through targeting γ-catenin in endothelial cells
MicroRNA-939 governs vascular integrity and angiogenesis through targeting γ-catenin in endothelial cells
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DOI：
10.1016/j.bbrc.2017.01.085
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发表时间：
2017-02-26
影响因子：
3.1
通讯作者：
Li, Xinming
中科院分区：
文献类型：
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作者：
Hou, Shiqiang;Fang, Ming;Li, Xinming
冠状动脉侧支循环（CCC）在冠状动脉阻塞的情况下起着自然旁路的作用，它显著改善了冠状动脉疾病（CAD）患者的预后。microRNA（miRNAs）参与多种生理和病理过程，包括CCC生长中的血管生成。miRNA-939（miR-939）在血管生成中的作用仍不清楚。本研究旨在探讨miR-939在冠心病患者中的表达及其在血管生成中的作用。我们的研究结果首次表明，与CCC较差的患者相比，CCC充足的患者循环miR-939的表达下调。原代人脐静脉内皮细胞（HUVECs）中过表达miR-939可显著抑制HUVECs的增殖、粘附和管腔形成，但促进细胞迁移。相比之下，miR-939敲低产生了相反的效果。我们进一步确定了γ-catenin是miR-939通过翻译抑制作用的新靶点，它可以挽救miR-939在HUVECs中的作用。总之，本研究揭示了循环miR-939的表达在具有足够CCC的CAD患者中下调。MiR-939通过直接靶向γ-连环蛋白破坏血管完整性并抑制血管生成。它为CAD提供了潜在的生物标志物和治疗靶点。(C)2017爱思唯尔公司All rights reserved.
Coronary collateral circulation (CCC) functions as a natural bypass in the event of coronary obstruction, which markedly improves prognosis in patients with coronary artery disease (CAD). MicroRNAs (miRNAs) have been implicated in multiple physiological and pathological processes, including angiogenesis involved in CCC growth. The roles that miRNA-939 (miR-939) plays in angiogenesis remain largely unknown. We conducted this study to explore the expression of miR-939 in CAD patients and its role in angiogenesis. For the first time, our results indicated that the expression of circulating miR-939 was down-regulated in patients with sufficient CCC compared with patients with poor CCC. Overexpression of miR-939 in primary human umbilical vein endothelial cells (HUVECs) significantly inhibited the proliferation, adhesion and tube formation, but promoted the migration of cells. In contrast, miR-939 knockdown exerted reverse effects. We further identified that gamma-catenin was a novel target of miR-939 by translational repression, which could rescue the effects of miR-939 in HUVECs. In summary, this study revealed that the expression of circulating miR-939 was down-regulated in CAD patients with sufficient CCC. MiR-939 abolished vascular integrity and repressed angiogenesis through directly targeting gamma-catenin. It provided a potential biomarker and a therapeutic target for CAD. (C) 2017 Elsevier Inc. All rights reserved.