1 Computational and RNA Biology, Department of Biology, Faculty of Science, Københavns Universitet2 Lund Group, BRIC Research Groups, BRIC, Københavns Universitet3 unknown4 Department of Mathematical Sciences, Faculty of Science, Københavns Universitet5 Lund Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet6 Lund Group, BRIC Research Groups, BRIC, Københavns Universitet7 Department of Mathematical Sciences, Faculty of Science, Københavns Universitet8 Computational and RNA Biology, Department of Biology, Faculty of Science, Københavns Universitet9 Lund Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet
Endothelial cells growing in high glucose-containing medium show reduced cell proliferation and in vitro angiogenesis. Evidence suggests that the molecular pathways leading to these cellular responses are controlled by microRNAs, endogenous post-transcriptional regulators of gene expression. To identify the microRNAs and their targeted genes involved in the glucose responses, we performed the miRNA signature of Human Umbelical Vein Endothelial Cells (HUVECs) exposed and unexposed to high glucose. Among differentially expressed microRNAs, we analysed miR-492 and showed that its overexpression was able to reduce proliferation, migration and tube formation of HUVEC. These effects were accompanied by the down-regulation of eNOS, a key regulator of the endothelial cell function. We showed that eNOS was indirectly down-regulated by miR-492 and we discovered that miR-492 was able to bind mRNAs involved in proliferation, migration, tube formation and regulation of eNOS activity and expression. Moreover, we found that miR-492 decreased VEGF expression in HUVEC and impaired in vivo angiogenesis in a tumour xenograft model, suggesting a role also in modulating the secretion of pro-angiogenic factors. Taken together, the data indicate that miR-492 exerts a potent anti-angiogenic activity in endothelial cells and therefore miR-492 seems a promising tool for anti-angiogenic therapy.
Journal of Cellular and Molecular Medicine, 2013, Vol 17, Issue 8, p. 1006-15