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

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 numbe...

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Main Authors: Bridge, G, Monteiro, R, Henderson, S, Emuss, V, Lagos, D, Georgopoulou, D, Patient, R, Boshoff, C
Format: Journal article
Language:English
Published: 2012
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author Bridge, G
Monteiro, R
Henderson, S
Emuss, V
Lagos, D
Georgopoulou, D
Patient, R
Boshoff, C
author_facet Bridge, G
Monteiro, R
Henderson, S
Emuss, V
Lagos, D
Georgopoulou, D
Patient, R
Boshoff, C
author_sort Bridge, G
collection OXFORD
description 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.
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spelling oxford-uuid:06b714c2-c110-4902-a826-1d1f13e2267c2022-03-26T09:03:57ZThe microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:06b714c2-c110-4902-a826-1d1f13e2267cEnglishSymplectic Elements at Oxford2012Bridge, GMonteiro, RHenderson, SEmuss, VLagos, DGeorgopoulou, DPatient, RBoshoff, CDelta-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.
spellingShingle Bridge, G
Monteiro, R
Henderson, S
Emuss, V
Lagos, D
Georgopoulou, D
Patient, R
Boshoff, C
The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
title The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
title_full The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
title_fullStr The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
title_full_unstemmed The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
title_short The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
title_sort microrna 30 family targets dll4 to modulate endothelial cell behavior during angiogenesis
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