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

JL Zhao, DS Rao, MP Boldin… - Proceedings of the …, 2011 - National Acad Sciences
JL Zhao, DS Rao, MP Boldin, KD Taganov, RM O'Connell, D Baltimore
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences