Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9184-9. doi: 10.1073/pnas.1105398108. Epub 2011 May 16.
MicroRNA miR-146a has been implicated as a negative feedback regulator of NF-κB 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-κB-regulated genes and tumors have higher nuclear p65. Genetic ablation of NF-κB p50 suppresses the myeloproliferation, showing that dysregulation of NF-κB is responsible for the myeloproliferative disease.
miR-146a 是 NF-κB 激活的负反馈调节因子。在 C57BL/6 小鼠中敲除 miR-146a 基因，会导致组织学和免疫表型定义明确的髓肉瘤和一些淋巴瘤。肉瘤可移植到免疫功能受损的宿主中，表明它们是真正的恶性肿瘤。动物的骨髓中还表现出慢性骨髓增生。脾脏和骨髓细胞显示 NF-κB 调节基因的转录增加，肿瘤细胞核中 p65 升高。NF-κB p50 的遗传缺失抑制骨髓增生，表明 NF-κB 的失调是骨髓增生性疾病的原因。
