miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells.
Cancer Cell, 2008/11/04;14(5):382-93.
Würdinger T[1], Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM
Affiliations
PMID: 18977327DOI: 10.1016/j.ccr.2008.10.005
Impact factor: 38.585
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.
MeSH terms
Angiogenesis Inhibitors; Animals; Base Sequence; Blotting, Western; Brain Neoplasms; Cell Movement; Cells, Cultured; Endosomal Sorting Complexes Required for Transport; Endothelium, Vascular; Fluorescent Antibody Technique; Glioma; Hepatocyte Growth Factor; Humans; Kidney; Luciferases; Magnetic Resonance Imaging; Mice; MicroRNAs; Molecular Sequence Data; Neovascularization, Pathologic; Oligonucleotides; Phosphoproteins; RNA, Messenger; RNA, Small Interfering; Receptor, Platelet-Derived Growth Factor beta; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid; Signal Transduction; Umbilical Veins; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays
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