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

Research output: Contribution to journalArticle

Authors

  • Gemma Bridge
  • Stephen Henderson
  • Victoria Emuss
  • Dimitris Lagos
  • Dimitra Georgopoulou
  • Roger Patient
  • Chris Boshoff

Colleges, School and Institutes

External organisations

  • UCL Cancer Institute
  • Weatherall Institute of Molecular Medicine
  • YORK UNIVERSITY (U.K.)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)5063-5072
Number of pages10
JournalBlood
Volume120
Issue number25
Publication statusPublished - 13 Dec 2012