title: MicroRNA-939 governs vascular integrity and angiogenesis through targeting γ-catenin in endothelial cells.
abstract: 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 γ-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 γ-catenin. It provided a potential biomarker and a therapeutic target for CAD.
authors.affiliation: Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Cardiology, Zhoupu Hospital, Shanghai 201318, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Cardiology, Zhoupu Hospital, Shanghai 201318, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Zhoupu Hospital, Shanghai 201318, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Zhoupu Hospital, Shanghai 201318, China. Electronic address: yylliwaly@sina.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Tongji University School of Medicine, Shanghai 200092, China; Department of Cardiology, Zhoupu Hospital, Shanghai 201318, China. Electronic address: zphospitallxx@126.com.
authors.forename: Xinming
authors.initials: X
authors.lastname: Li
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051185:gamma Catenin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C000604729:MIRN939 microRNA, human; D035683:MicroRNAs; D051185:gamma Catenin
keywords: Angiogenesis; Coronary collateral circulation; MicroRNA-939; Vascular integrity; γ-catenin