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

被引:726
作者
Boldin, Mark P. [1 ,2 ]
Taganov, Konstantin D. [1 ,2 ]
Rao, Dinesh S. [1 ,3 ]
Yang, Lili [1 ]
Zhao, Jimmy L. [1 ]
Kalwani, Manorama [1 ]
Garcia-Flores, Yvette [1 ]
Luong, Mui [1 ]
Devrekanli, Asli [1 ]
Xu, Jessica [2 ]
Sun, Guizhen [2 ]
Tay, Jia [2 ]
Linsley, Peter S. [2 ]
Baltimore, David [1 ]
机构
[1] CALTECH, Div Biol, Pasadena, CA 91125 USA
[2] Regulus Therapeut, San Diego, CA 92121 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
NF-KAPPA-B; ACUTE MYELOBLASTIC-LEUKEMIA; RECEPTOR-ASSOCIATED KINASE; CYTOKINE GENE-CLUSTER; TUMOR-NECROSIS-FACTOR; DEFECTIVE INTERLEUKIN-1; MYELOID-LEUKEMIA; IMMUNE-RESPONSES; EXPRESSION; MICRORNA;
D O I
10.1084/jem.20101823
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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), similar to 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.
引用
收藏
页码:1189 / 1201
页数:13
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