MiR-17 and -20a target the neuron-derived orphan receptor-1 (NOR-1) in vascular endothelial cells
Sambri, Irene (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Crespo, Javier (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Aguiló, Silvia (Institut d'Investigació Biomèdica Sant Pau)
Ingrosso, Diego (Second University of Naples)
Rodríguez, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Martínez-González, José (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2015
Abstract:	Neuron-derived orphan receptor-1 (NOR-1) plays a major role in vascular biology by controlling fibroproliferative and inflammatory responses. Because microRNAs (miRNAs) have recently emerged as key players in the regulation of gene expression in the vasculature, here we have investigated the regulation of NOR-1 by miRNAs in endothelial cells. Computational algorithms suggest that NOR-1 could be targeted by members of the miR-17 family. Accordingly, ectopic over-expression of miR-17 or miR-20a in endothelial cells using synthetic premiRNAs attenuated the up-regulation of NOR-1 expression induced by VEGF (as evidenced by real time PCR, Western blot and immunocitochemistry). Conversely, the antagonism of these miRNAs by specific antagomirs prevented the down-regulation of NOR-1 promoted by miR-17 or miR-20a in VEGF-stimulated cells. Disruption of the miRNANOR- 1 mRNA interaction using a custom designed target protector evidenced the selectivity of these responses. Further, luciferase reporter assays and seed-sequence mutagenesis confirmed that miR-17 and -20a bind to NOR-1 3'-UTR. Finally, miR-17 and -20a ameliorated the up-regulation of VCAM-1 mediated by NOR-1 in VEGF-stimulated cells. Therefore, miR-17 and -20a target NOR-1 thereby regulating NOR-1-dependent gene expression.
Grants:	Ministerio de Economía y Competitividad SAF2012-40127 Ministerio de Economía y Competitividad RD12/0042/0053 Ministerio de Economía y Competitividad PI12/01952
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 10 Núm. 11 (january 2015) , p. e0141932, ISSN 1932-6203

DOI: 10.1371/journal.pone.0141932
PMID: 26600038

13 p, 1.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles