miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells
View/ Open
Author
Würdinger, Thomas
Tannous, Bakhos A.
Saydam, Okay
Skog, Johan
Grau, Stephan
Soutschek, Jürgen
Weissleder, Ralph
Breakefield, Xandra O.
Krichevsky, Anna M.
Published Version
https://doi.org/10.1016/j.ccr.2008.10.005Metadata
Show full item recordCitation
Würdinger, 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.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 PDGFR beta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384308
Collections
- HMS Scholarly Articles [17714]
Contact administrator regarding this item (to report mistakes or request changes)