miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells
Tannous, Bakhos A.
Breakefield, Xandra O.
Krichevsky, Anna M.
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CitationWürdinger, Thomas, Bakhos A. Tannous, Okay Saydam, Johan Skog, Stephan Grau, Jürgen Soutschek, Ralph Weissleder, Xandra O. Breakefield, and Anna M. Krichevsky. 2008. “miR-296 Regulates Growth Factor Receptor Overexpression in Angiogenic Endothelial Cells.” Cancer Cell 14 (5): 382–93. https://doi.org/10.1016/j.ccr.2008.10.005.
AbstractA 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 PDGFR beta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384308
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