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miR-17 and -20a Target the Neuron-Derived Orphan Receptor-1 (NOR-1) in Vascular Endothelial Cells
- Source :
- PLoS ONE, Vol 10, Iss 11, p e0141932 (2015), PLoS ONE, PLoS One, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, Instituto Cervantes
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 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 3â²-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.
- Subjects :
- Molecular Sequence Data
Down-Regulation
lcsh:Medicine
Biology
Downregulation and upregulation
Western blot
Nuclear Receptor Subfamily 4, Group A, Member 3
microRNA
Gene expression
medicine
Human Umbilical Vein Endothelial Cells
Humans
RNA, Messenger
lcsh:Science
Transcription factor
3' Untranslated Regions
Regulation of gene expression
Multidisciplinary
Biochemistry, Genetics and Molecular Biology (all)
Binding Sites
medicine.diagnostic_test
Base Sequence
Three prime untranslated region
lcsh:R
Computational Biology
Molecular biology
Neuron-derived orphan receptor 1
Cell biology
MicroRNAs
Agricultural and Biological Sciences (all)
lcsh:Q
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....b70a1c16007b9831b7b54817198cd106