1. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice.
- Author
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Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J, Sun G, Tay J, Linsley PS, and Baltimore D
- Subjects
- 3' Untranslated Regions, Animals, Cell Proliferation, Cell Transformation, Neoplastic, Female, Humans, Inflammation, Interleukin-1 Receptor-Associated Kinases metabolism, Lipopolysaccharides metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Neoplasms genetics, RNA Processing, Post-Transcriptional, TNF Receptor-Associated Factor 6 metabolism, Up-Regulation, Autoimmunity, MicroRNAs genetics, Neoplasms immunology
- 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.
- Published
- 2011
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