Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/105828
Title: NF-κB-direct activation of microRNAs with repressive effects on monocyte-specific genes is critical for osteoclast differentiation
Author: Rica, Lorenzo de la
García Gómez, Antonio
Comet, Natalia R.
Rodríguez-Ubreva, Javier
Ciudad, Laura
Vento Tormo, Roser
Company, Carlos
Álvarez-Errico, Damiana
García, Mireia
Gómez Vaquero, Carmen
Ballestar Tarín, Esteban
Keywords: Micro RNAs
Genètica mèdica
Diferenciació cel·lular
Artritis reumatoide
Metàstasi
Càncer d'ossos
MicroRNAs
Medical genetics
Cell diferentiation
Rheumatoid arthritis
Metastasis
Bones cancer
Issue Date: 5-Jan-2015
Publisher: BioMed Central
Abstract: Monocyte-to-osteoclast conversion is a unique terminal differentiation process that is exacerbated in rheumatoid arthritis and bone metastasis. The mechanisms implicated in upregulating osteoclast-specific genes involve transcription factors, epigenetic regulators and microRNAs (miRNAs). It is less well known how downregulation of osteoclast-inappropriate genes is achieved. RESULTS: In this study, analysis of miRNA expression changes in osteoclast differentiation from human primary monocytes revealed the rapid upregulation of two miRNA clusters, miR-212/132 and miR-99b/let-7e/125a. We demonstrate that they negatively target monocyte-specific and immunomodulatory genes like TNFAIP3, IGF1R and IL15. Depletion of these miRNAs inhibits osteoclast differentiation and upregulates their targets. These miRNAs are also upregulated in other inflammatory monocytic differentiation processes. Most importantly, we demonstrate for the first time the direct involvement of Nuclear Factor kappa B (NF-κB) in the regulation of these miRNAs, as well as with their targets, whereby NF-κB p65 binds the promoters of these two miRNA clusters and NF-κB inhibition or depletion results in impaired upregulation of their expression. CONCLUSIONS:Our results reveal the direct involvement of NF-κB in shutting down certain monocyte-specific genes, including some anti-inflammatory activities, through a miRNA-dependent mechanism for proper osteoclast differentiation.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s13059-014-0561-5
It is part of: Genome Biology, 2015, vol. 16, num. 2, p. 1-17
Related resource: https://doi.org/10.1186/s13059-014-0561-5
URI: http://hdl.handle.net/2445/105828
ISSN: 1465-6906
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)

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