ZFIN ID: ZDB-PUB-121102-21
The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis
Bridge, G., Monteiro, R., Henderson, S., Emuss, V., Lagos, D., Georgopoulou, D., Patient, R., and Boshoff, C.
Date: 2012
Source: Blood   120(25): 5063-5072 (Journal)
Registered Authors: Patient, Roger K.
Keywords: none
MeSH Terms:
  • Animals
  • Base Sequence
  • Cell Line
  • Embryo, Nonmammalian/blood supply
  • Embryo, Nonmammalian/metabolism
  • Endothelial Cells/cytology*
  • Endothelial Cells/metabolism
  • Endothelial Cells/virology
  • Gene Expression Regulation, Developmental
  • Herpesviridae Infections/virology
  • Herpesvirus 8, Human/physiology
  • Host-Pathogen Interactions
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics*
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism
  • MicroRNAs/genetics*
  • MicroRNAs/metabolism
  • Neovascularization, Physiologic*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A/genetics
  • Zebrafish/embryology
PubMed: 23086751 Full text @ Blood

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.