title: MicroRNA 329 suppresses angiogenesis by targeting CD146.
abstract: CD146, an endothelial biomarker, has been shown to be aberrantly upregulated during pathological angiogenesis and functions as a coreceptor for vascular endothelial growth factor receptor 2 (VEGFR-2) to promote disease progression. However, the regulatory mechanisms of CD146 expression during angiogenesis remain unclear. Using a microRNA screening approach, we identified a novel negative regulator of angiogenesis, microRNA 329 (miR-329), that directly targeted CD146 and inhibited CD146-mediated angiogenesis in vitro and in vivo. Endogenous miR-329 expression was downregulated by VEGF and tumor necrosis factor alpha (TNF-α), resulting in the elevation of CD146 in endothelial cells. Upregulation of CD146 facilitated an endothelial response to VEGF-induced SRC kinase family (SKF)/p38 mitogen-activated protein kinase (MAPK)/NF-κB activation and consequently promoted endothelial cell migration and tube formation. Our animal experiments showed that treatment with miR-329 repressed excessive CD146 expression on blood vessels and significantly attenuated neovascularization in a mouse model of pathological angiogenesis. Our findings provide the first evidence that CD146 expression in angiogenesis is regulated by miR-329 and suggest that miR-329 could present a potential therapeutic tool for the treatment of angiogenic diseases.
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, CAS-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yongting
authors.initials: Y
authors.lastname: Luo
authors.forename: Hongxia
authors.initials: H
authors.lastname: Duan
authors.forename: Shu
authors.initials: S
authors.lastname: Xing
authors.forename: Jianlin
authors.initials: J
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Dongling
authors.initials: D
authors.lastname: Yang
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.forename: Xiyun
authors.initials: X
authors.lastname: Yan
mesh_terms: D000818:Animals; D001483:Base Sequence; D051929:CD146 Antigen / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D015861:Retinal Neovascularization / Q000209:etiology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human; C584396:MIRN329 microRNA, human; C584397:MIRN329 microRNA, mouse; C497903:Mcam protein, mouse; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A