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Title: | NF-κB-direct activation of microRNAs with repressive effects on monocyte-specific genes is critical for osteoclast differentiation |
Author: | Rica Lázaro, 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 |
URI: | http://hdl.handle.net/2445/105828 |
Related resource: | https://doi.org/10.1186/s13059-014-0561-5 |
ISSN: | 1465-6906 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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