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

  • Author(s): Boldin, Mark P;
  • Taganov, Konstantin D;
  • Rao, Dinesh S;
  • Yang, Lili;
  • Zhao, Jimmy L;
  • Kalwani, Manorama;
  • Garcia-Flores, Yvette;
  • Luong, Mui;
  • Devrekanli, Asli;
  • Xu, Jessica;
  • Sun, Guizhen;
  • Tay, Jia;
  • Linsley, Peter S;
  • Baltimore, David
  • et al.
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.

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