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Cancer Cell. 2008 Nov 4;14(5):382-93. doi: 10.1016/j.ccr.2008.10.005.

miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells.

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  • 1Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02115, USA.

Abstract

A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells. Here, we demonstrate that a small regulatory microRNA, miR-296, has a major role in this process. Glioma cells and angiogenic growth factors elevate the level of miR-296 in primary human brain microvascular endothelial cells in culture. The miR-296 level is also elevated in primary tumor endothelial cells isolated from human brain tumors compared to normal brain endothelial cells. Growth factor-induced miR-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor receptors VEGFR2 and PDGFRbeta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo.

PMID:
18977327
[PubMed - indexed for MEDLINE]
PMCID:
PMC2597164
Free PMC Article

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