title: The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
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.
authors.affiliation: Cancer Research UK Viral Oncology Group, UCL Cancer Institute, University College London, London, United Kingdom.
authors.forename: Gemma
authors.initials: G
authors.lastname: Bridge
authors.forename: Rui
authors.initials: R
authors.lastname: Monteiro
authors.forename: Stephen
authors.initials: S
authors.lastname: Henderson
authors.forename: Victoria
authors.initials: V
authors.lastname: Emuss
authors.forename: Dimitris
authors.initials: D
authors.lastname: Lagos
authors.forename: Dimitra
authors.initials: D
authors.lastname: Georgopoulou
authors.forename: Roger
authors.initials: R
authors.lastname: Patient
authors.forename: Chris
authors.initials: C
authors.lastname: Boshoff
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D018507:Gene Expression Regulation, Developmental; D006566:Herpesviridae Infections / Q000821:virology; D019288:Herpesvirus 8, Human / Q000502:physiology; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D015027:Zebrafish / Q000196:embryology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C585572:MIRN30 microRNA, zebrafish; C546086:MIRN30b microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; C064045:delta protein