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miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

Boldin, Mark P. and Taganov, Konstantin D. and Rao, Dinesh S. and Yang, Lili and Zhao, Jimmy L. and Kalwani, Manorama and Garcia-Flores, Yvette and Luong, Mui and Devrekanli, Asli and Xu, Jessica and Sun, Guizhen and Tay, Jia and Linsley, Peter S. and Baltimore, David (2011) miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. Journal of Experimental Medicine, 208 (6). pp. 1189-1201. ISSN 0022-1007. PMCID PMC3173243. https://resolver.caltech.edu/CaltechAUTHORS:20110627-164327215

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Abstract

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ~22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1084/jem.20101823DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173243/PubMed CentralArticle
ORCID:
AuthorORCID
Boldin, Mark P.0000-0003-4593-0669
Rao, Dinesh S.0000-0002-0794-9337
Baltimore, David0000-0001-8723-8190
Additional Information:© 2011 Boldin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). Submitted: 1 September 2010; Accepted: 14 April 2011. Published May 9, 2011. We thank Shirley Pease and other members of the Caltech Transgenic Core Facility for their technical support. We thank Sergei Grivennikov for critical reading of the manuscript and Matthew Liabson for the generation of 3' UTR reporter constructs. This work was supported by National Institutes of Health grant 5R01AI079243-02 and career development award 5K08CA133521 (to D.S. Rao). M.P. Boldin, K.D. Taganov, J. Xu, G. Sun, J. Tay, and P.S. Linsley are employees and shareholders of Regulus Therapeutics, a biotech company developing miRNA-based drugs. D. Baltimore is a director and Chairman of the Scientific Advisory board of the same company. Author contributions: M.P. Boldin, K.D. Taganov, D.S. Rao, L. Yang, J.L. Zhao, and D. Baltimore designed the study, analyzed data, and wrote the paper. M.P. Boldin, K.D. Taganov, D.S. Rao, L. Yang, M. Kalwani, Y. Garcia-Flores, M. Luong, A. Devrekanli, J. Xu, G. Sun, and J. Tay collected data. P.S. Linsley performed bioinformatical analyses and wrote the paper.
Funders:
Funding AgencyGrant Number
NIH5R01AI079243-02
NIH5K08CA133521
Subject Keywords:AML, acute myeloid leukemia; BMDM, BM-derived macrophage; MDS, myelodysplastic syndrome; miRNA, microRNA; mRNA, messenger RNA; qRT-PCR, quantitative RT-PCR; snRNA, small nuclear RNA; TLR, Tolllike receptor; UTR, untranslated region.
Issue or Number:6
PubMed Central ID:PMC3173243
Record Number:CaltechAUTHORS:20110627-164327215
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110627-164327215
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24229
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:28 Jun 2011 18:31
Last Modified:08 Jul 2020 22:02

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