| First Author | Wang L | Year | 2014 |
| Journal | Cell Stem Cell | Volume | 15 |
| Issue | 1 | Pages | 51-65 |
| PubMed ID | 24996169 | Mgi Jnum | J:218495 |
| Mgi Id | MGI:5617679 | Doi | 10.1016/j.stem.2014.04.021 |
| Citation | Wang L, et al. (2014) Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in an NF-kappaB-dependent manner. Cell Stem Cell 15(1):51-65 |
| abstractText | The 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 kappaB (NF-kappaB) inhibitor kappaB-Ras1, NF-kappaB 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/kappaB-Ras1/NF-kappaB axis regulates the inflammatory state of the BM niche and affects the development of myeloproliferative disorders. |
