title: miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice.
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.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. mboldin@coh.org
authors.forename: Mark P
authors.initials: MP
authors.lastname: Boldin
authors.forename: Konstantin D
authors.initials: KD
authors.lastname: Taganov
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Rao
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: Jimmy L
authors.initials: JL
authors.lastname: Zhao
authors.forename: Manorama
authors.initials: M
authors.lastname: Kalwani
authors.forename: Yvette
authors.initials: Y
authors.lastname: Garcia-Flores
authors.forename: Mui
authors.initials: M
authors.lastname: Luong
authors.forename: Asli
authors.initials: A
authors.lastname: Devrekanli
authors.forename: Jessica
authors.initials: J
authors.lastname: Xu
authors.forename: Guizhen
authors.initials: G
authors.lastname: Sun
authors.forename: Jia
authors.initials: J
authors.lastname: Tay
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D015551:Autoimmunity; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D007249:Inflammation; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D012323:RNA Processing, Post-Transcriptional; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D008070:Lipopolysaccharides; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D048029:TNF Receptor-Associated Factor 6; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse