Wang, LinZhang, HuajiaRodriguez, SoniaCao, LiyunParish, JonathanMumaw, ChristenZollman, AmyKamocka, GosiaMu, JianChen, Danny Z.Srour, Edward F.Chitteti, Brahmananda R.HogenEsch, HarmTu, XiaolinBellido, Teresita M.Boswell, ScottManshouri, TaghiVerstovsek, SrdanYoder, Mervin C.Kapur, ReubenCardoso, Angelo A.Carlesso, Nadia2016-04-112016-04-112014-07-03Wang, L., Zhang, H., Rodriguez, S., Cao, L., Parish, J., Mumaw, C., … Carlesso, N. (2014). Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in an NF-κB dependent manner. Cell Stem Cell, 15(1), 51–65. http://doi.org/10.1016/j.stem.2014.04.0211875-9777https://hdl.handle.net/1805/9245The microRNA miR-155 has been implicated in regulating inflammatory responses and tumorigenesis, but its precise role in linking inflammation and cancer has remained elusive. Here, we identify a connection between miR-155 and Notch signaling in this context. Loss of Notch signaling in the bone marrow (BM) niche alters hematopoietic homeostasis and leads to lethal myeloproliferative-like disease. Mechanistically, Notch signaling represses miR-155 expression by promoting binding of RBPJ to the miR-155 promoter. Loss of Notch/RBPJ signaling upregulates miR-155 in BM endothelial cells, leading to miR-155-mediated targeting of the nuclear factor κB (NF-κB) inhibitor κB-Ras1, NF-κB activation, and increased proinflammatory cytokine production. Deletion of miR-155 in the stroma of RBPJ(-/-) mice prevented the development of myeloproliferative-like disease and cytokine induction. Analysis of BM from patients carrying myeloproliferative neoplasia also revealed elevated expression of miR-155. Thus, the Notch/miR-155/κB-Ras1/NF-κB axis regulates the inflammatory state of the BM niche and affects the development of myeloproliferative disorders.en-USPublisher PolicyBone MarrowphysiologyHematologic NeoplasmsgeneticsMicroRNAsmetabolismMyeloproliferative DisordersReceptors, NotchArticle