miRNA analysis of HBMVECs exposed or unexposed to U87 glioma cells. Homo sapiens

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-ß. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo. Keywords: comparitive miRNA analysis Overall design: 3 biological replicates (HBMVECs) are compared to 3 biological replicates (HBMVECs exposed to U87 glioma cells)