The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.

Journal article

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 up-regulated dll4 and synergized with Vegfa signaling knockdown to inhibit angiogenesis. Furthermore, restoration of miR-30b or miR-30c expression during Kaposi 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.

Authors: Bridge, G; Monteiro, R; Henderson, S; Emuss, V; Lagos, D

• Publication status: Published
• Journal: Blood
• Volume: 120
• Issue: 25
• Pages: 5063-5072
• Publication date: 2012-12-01
• DOI: 10.1182/blood-2012-04-423004
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Cell Line; Animals; Intracellular Signaling Peptides and Proteins; Vascular Endothelial Growth Factor A; Host-Pathogen Interactions; Gene Expression Regulation, Developmental; Embryo, Nonmammalian; Zebrafish; Humans; Base Sequence; Endothelial Cells; Up-Regulation; Herpesviridae Infections; Herpesvirus 8, Human; MicroRNAs; Human Umbilical Vein Endothelial Cells; Membrane Proteins; Neovascularization, Physiologic