MicroRNA 329 suppresses angiogenesis by targeting CD146

Ping Wang; Yongting Luo; Hongxia Duan; Shu Xing; Jianlin Zhang; Di Lu; Jing Feng; Dongling Yang; Lina Song; Xiyun Yan

doi:10.1128/MCB.00343-13

MicroRNA 329 suppresses angiogenesis by targeting CD146

Mol Cell Biol. 2013 Sep;33(18):3689-99. doi: 10.1128/MCB.00343-13. Epub 2013 Jul 22.

Authors

Ping Wang¹, Yongting Luo, Hongxia Duan, Shu Xing, Jianlin Zhang, Di Lu, Jing Feng, Dongling Yang, Lina Song, Xiyun Yan

Affiliation

¹ 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.

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あるふぁ), 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-κかっぱB 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
CD146 Antigen / genetics
CD146 Antigen / physiology
Cells, Cultured
Disease Models, Animal
Endothelial Cells / immunology
Endothelial Cells / physiology
Female
Gene Expression Regulation
HEK293 Cells
Human Umbilical Vein Endothelial Cells
Humans
Mice
Mice, Inbred C57BL
Mice, SCID
MicroRNAs / genetics
MicroRNAs / physiology*
Neovascularization, Pathologic / genetics*
Neovascularization, Pathologic / immunology
Neovascularization, Physiologic* / genetics
Neovascularization, Physiologic* / immunology
Retinal Neovascularization / etiology
Retinal Neovascularization / prevention & control
Tumor Necrosis Factor-alpha / physiology
Vascular Endothelial Growth Factor A / physiology

Substances

CD146 Antigen
MCAM protein, human
MIRN329 microRNA, human
MIRN329 microRNA, mouse
Mcam protein, mouse
MicroRNAs
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A