Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in an NF-κB-dependent manner.

Autor:	Wang L; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Zhang H; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Rodriguez S; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Cao L; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Parish J; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Mumaw C; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Zollman A; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Kamoka MM; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Mu J; Department of Computer Science and Engineering, University of Notre Dame, South Bend, IN 46556, USA., Chen DZ; Department of Computer Science and Engineering, University of Notre Dame, South Bend, IN 46556, USA., Srour EF; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Chitteti BR; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA., HogenEsch H; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA., Tu X; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Bellido TM; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Boswell HS; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Manshouri T; Leukemia Department, MD Anderson Cancer Center, Houston, TX 77030, USA., Verstovsek S; Leukemia Department, MD Anderson Cancer Center, Houston, TX 77030, USA., Yoder MC; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Kapur R; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Cardoso AA; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Carlesso N; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: ncarless@iu.edu.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2014 Jul 03; Vol. 15 (1), pp. 51-65.
DOI:	10.1016/j.stem.2014.04.021
Abstrakt:	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 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. (Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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