Bridge, G., Monteiro, R., Henderson, S., Emuss, V., Lagos, D., Georgopoulou, D., Patient, R., and Boshoff, C. (2012) The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 120(25):5063-5072.
Delta-like 4 (DLL4), a membrane-bound ligand belonging to the Notch signaling family, plays a fundamental role in vascular
development and angiogenesis. We identified a conserved microRNA family, miR-30, which targets DLL4. Overexpression of miR-30b in endothelial cells led to increased vessel number and length in an in vitro model of sprouting angiogenesis. Microinjection of miR-30 mimics into zebrafish embryos resulted in suppression of dll4 and subsequent excessive sprouting of intersegmental vessels and reduction in dorsal aorta diameter. Use of a target protector
against the miR-30 site within the dll4 3'UTR upregulated dll4 and synergized with Vegfa signaling knockdown to inhibit angiogenesis. Furthermore, restoration of miR-30b or -30c expression
during Kaposi's sarcoma herpesvirus (KSHV) infection attenuated viral induction of DLL4. Together these results demonstrate
that the highly conserved molecular targeting of DLL4 by the miR-30 family regulates angiogenesis.
