Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder

By Ryan M. O’Connell, D. Rao, Aadel A Chaudhuri, M. Boldin, K. Taganov, J. Nicoll, R. Paquette, David Baltimore. Journal of Experimental Medicine, 2008

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Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155–induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9f96783487cc3209f8e3e54a6f1a237da139217d

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Citations in the corpus

MicroRNAs in human cancer. (2013, background): “of miR-155 in bone marrow induced polyclonal pre-B cell proliferation progressing to B-cell leukemia or myeloproliferation in mice [ 175, 176 ] .”
MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development (2010, methodology): “0 as described previously (O’Connell et al., 2008), and the data were analyzed further with Rosetta Resolver software.”
miR2Disease: a manually curated database for microRNA deregulation in human disease (2008, background): “mentary sites in the 30-untranslated regions of target genes (2).”
Role of microRNAs in vascular diseases, inflammation, and angiogenesis. (2008, background): “miR-155 is induced in macrophages by cytokines such as TNFa and IFN-beta(66,67) and contributes to physiological granulocyte/monocyte expansion during inflammation.(68) In addition, miR-155 is required for B and T lymphocyte and dendritic cell function.”
MicroRNA control in the immune system: basic principles. (2009, background): “Induction of miR-155 expression by LPS could thus be a mechanism through which the immune system rapidly expands the myeloid cell population during inflammatory responses (O’Connell et al., 2008).”
Molecular Mechanisms That Influence the Macrophage M1–M2 Polarization Balance (2014, background): “While these functional miRNAs like miR-155 and miR-146 are induced by a variety of inflammatory stimuli, including LPS, TNFα, and IL-1β, they are instrumental in attenuating TLR4/IL-1R signaling pathways in monocytes and macrophages (79, 82, 83).”
microRNA regulation of inflammatory responses. (2012, background): “The overexpression of miR-155 produces a myeloproliferative disorder (MPD) that is highly reminiscent of inflammatory hematopoiesis, with reductions in the numbers of erythroid and B cells and a profound myeloid expansion (35).”
Inositol phosphatase SHIP1 is a primary target of miR-155 (2009, methodology): “Therefore, miR-155 repression of SHIP1 may prove to be a contributing factor to human MPDs and myeloid leukemias, where miR-155 has been shown to be over-expressed (7, 23).”
Biological functions of microRNAs: a review (2011, background): “Quite recently, O'Connell et al. [ 37 ] found increased expression of miR-155 in bone marrow blasts of leukemic patients bearing M4 or M5 subtypes of acute myeloid leukemia (AML).”
microRNAs and the immune response (2009, background): “A role for miR-155 was first suggested from the examination of bone marrow myeloid cells obtained from LPS exposed mice [15].”
miR-155 gene: a typical multifunctional microRNA. (2009, background): “In addition, C/EBPβ is a transcription factor which plays an important role during heamatopoietic cell growth and differentiation and has been found to be a potential target of miR-155 in in vivo AML development [46].”
MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. (2009, background): “155 (O’Connell et al., 2008), now suggests a mechanism that”
microRNAs in cancer (2013, background): “Quite recently, O’Connell and colleagues (127) found increased expression”