NF-κB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies

被引：334

作者：

Zhao, Jimmy L. ^{[1
]}

Rao, Dinesh S. ^{[1
,2
]}

Boldin, Mark P. ^{[3
]}

Taganov, Konstantin D. ^{[4
]}

O'Connell, Ryan M. ^{[1
]}

Baltimore, David ^{[1
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

[2] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA

[3] City Hope Natl Med Ctr, Dept Mol & Cellular Biol, Beckman Res Inst, Duarte, CA 91010 USA

[4] Regulus Therapeut Inc, San Diego, CA 92121 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 22期

基金：

美国国家卫生研究院;

关键词：

inflammation; cancer; myelofibrosis; noncoding RNA; IMMUNE-RESPONSES; MICRORNA SIGNATURES; TARGET; INFLAMMATION; ACTIVATION; MIR-146A; SYSTEM; CANCER; IRAK1; P50;

D O I：

10.1073/pnas.1105398108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

MicroRNA miR-146a has been implicated as a negative feedback regulator of NF-kappa B activation. Knockout of the miR-146a gene in C57BL/6 mice leads to histologically and immunophenotypically defined myeloid sarcomas and some lymphomas. The sarcomas are transplantable to immunologically compromised hosts, showing that they are true malignancies. The animals also exhibit chronic myeloproliferation in their bone marrow. Spleen and marrow cells show increased transcription of NF-kappa B-regulated genes and tumors have higher nuclear p65. Genetic ablation of NF-kappa B p50 suppresses the myeloproliferation, showing that dysregulation of NF-kappa B is responsible for the myeloproliferative disease.

引用

页码：9184 / 9189

页数：6

共 26 条

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