Regulation of vascular endothelial growth factor signaling by miR-200b
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Vascular endothelial growth factor (VEGF) signaling plays an important role in angiogenesis. In the VEGF signaling pathway, the key components are VEGF and its receptors, Flt-1 and KDR. In this study, we show that transfection of synthetic miR-200b reduced protein levels of VEGF, Flt-1, and KDR. In A549 cells, miR-200b targeted the predicted binding sites in the 3′-untranslated region (3′-UTR) of VEGF, Flt-1, and KDR as revealed by a luciferase reporter assay. When transfected with miR-200b, the ability of HUVECs to form a capillary tube on Matrigel and VEGF-induced phosphorylation of ERK1/2 were significantly reduced. Taken together, these results suggest that miR-200b negatively regulates VEGF signaling by targeting VEGF and its receptors and that miR-200b may have therapeutic potential as an angiogenesis inhibitor.
KeywordsFlt-1 KDR microRNA miR-200b VEGF VEGF signaling
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- van Solingen, C., Seghers, L., Bijkerk, R., Duijs, J.M., Roeten, M.K., van Oeveren-Rietdijk, A.M., Baelde, H.J., Monge, M., Vos, J.B., de Boer, H.C., et al. (2009). Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis. J. Cell. Mol. Med. 13, 1577–1585.PubMedCrossRefGoogle Scholar
- Wiklund, E.D., Bramsen, J.B., Hulf, T., Dyrskjøt, L., Ramanathan, R., Hansen, T.B., Villadsen, S.B., Gao, S., Ostenfeld, M.S., Borre, M., et al. (2010). Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int. J. Cancer 128, 1327–1334.CrossRefGoogle Scholar