Onco‐miR‐155 targets SHIP1 to promote TNFα‐dependent growth of B cell lymphomas

Pedersen, Irene M.; Otero, Dennis C.; Kao, Elaine; Miletic, Ana V.; Hother, Christoffer; Ralfkiær, Elisabeth; Rickert, Robert C.; Grønbæk, Kirsten; David, Michael

doi:10.1002/emmm.200900028

Cited by 193 publications

(147 citation statements)

References 28 publications

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“…Here we report for the first time that chronic alcohol treatment increases miR-155 levels in macrophages both in vitro and in vivo. miR-155 levels were increased upon LPS stimulation, and it has been hypothesized that its enhanced expression further augments TNF␣ secretion (5,27). Our novel observation demonstrates that chronic alcohol exposure augments TNF␣ production via miR-155 in liver macrophages.…”

Section: Discussionmentioning

confidence: 55%

Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor α (TNFα) Production via Increased mRNA Half-life in Alcoholic Liver Disease

Bala¹,

Marcos²,

Kodys

et al. 2011

Journal of Biological Chemistry

370

342

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Activation of Kupffer cells (KCs) by gut-derived lipopolysaccharide (LPS) and Toll-Like Receptors 4 (TLR4)-LPS-mediatedincrease in TNF␣ production has a central role in the pathogenesis of alcoholic liver disease. Micro-RNA (miR)-125b, miR-146a, and miR-155 can regulate inflammatory responses to LPS. Here we evaluated the involvement of miRs in alcoholinduced macrophage activation. Chronic alcohol treatment in vitro resulted in a time-dependent increase in miR-155 but not miR-125b or miR-146a levels in RAW 264.7 macrophages. Furthermore, alcohol pretreatment augmented LPS-induced miR-155 expression in macrophages. We found a linear correlation between alcohol-induced increase in miR-155 and TNF␣ induction. In a mouse model of alcoholic liver disease, we found a significant increase in both miR-155 levels and TNF␣ production in isolated KCs when compared with pairfed controls. The mechanistic role of miR-155 in TNF␣ regulation was indicated by decreased TNF␣ levels in alcohol-treated macrophages after inhibition of miR-155 and by increased TNF␣ production after miR-155 overexpression, respectively. We found that miR-155 affected TNF␣ mRNA stability because miR-155 inhibition decreased whereas miR-155 overexpression increased TNF␣ mRNA half-life. Using the NF-B inhibitors, MG-132 or Bay11-7082, we demonstrated that NF-B activation mediated the up-regulation of miR-155 by alcohol in KCs. In conclusion, our novel data demonstrate that chronic alcohol consumption increases miR-155 in macrophages via NF-B and the increased miR-155 contributes to alcohol-induced elevation in TNF␣ production via increased mRNA stability.

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Section: Discussionmentioning

confidence: 55%

Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor α (TNFα) Production via Increased mRNA Half-life in Alcoholic Liver Disease

Bala¹,

Marcos²,

Kodys

et al. 2011

Journal of Biological Chemistry

370

342

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“…We hypothesized that the loss of SHIP-1 might also be due to translational repression by miRs. miR-155 has recently been shown to suppress SHIP-1 expression by binding to its 3 0 untranslated region (UTR) (Costinean et al, 2009;O'Connell et al, 2009;Pedersen et al, 2009;Yamanaka et al, 2009). Three different internet-based miR prediction programs (http://www.microrna.org, http://www.targetscan.org, and http://mirnamap.mbc.nctu.edu.tw) predicted that SHIP-1 could be targeted not only by miR-155 but also by miR-210.…”

Section: Resultsmentioning

confidence: 99%

“…Increased levels of miR-155 were also found among high-risk, not low-risk, MDS patients (Pons et al, 2009). Downregulation of SHIP-1 expression by miR-155 activates the PI 3 0 kinase/Akt pathway (Costinean et al, 2009;Pedersen et al, 2009 (Rosenfeld and List, 2000). Aberrant expression of miR-155 has recently been found in natural killer leukemia/lymphoma cells that display increased level of phospho-Akt (Yamanaka et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155

et al. 2012

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The myelodysplastic syndromes (MDSs) comprise a group of disorders characterized by multistage progression from cytopenias to acute myeloid leukemia (AML). They display exaggerated apoptosis in early stages, but lose this behavior during evolution to AML. The molecular basis for loss of apoptosis is unknown. To investigate this critical event, we analyzed phosphatidylinositol (PI) 3 0 kinase signaling, implicated as a critical pathway of cell survival control in epithelial and hematological malignancies. PI 3 0 kinase activates Akt through its production of 3 0 phosphoinositides. In turn, the phosphoinositides are dephosphorylated by two lipid phosphatases, PTEN and SHIP-1, in myeloid cells. We studied primary MDS-enriched bone marrow cells and bone marrow sections by western blotting, immunohistochemistry, immunocytochemistry and quantitative PCR for components of the SHIP/PTEN/PI 3 0 kinase signaling circuit. We reported constitutively activated Akt, variable levels of PTEN and uniformly decreased SHIP-1 expression in MDS progenitor cells. Overexpression of SHIP-1, but not the phosphatase-deficient form, inhibited myeloid leukemic growth. Levels of microRNA (miR)-210 and miR-155 transcripts, which target SHIP-1, were increased in CD34 þ MDS cells compared with their normal counterparts. Direct binding of miR-210 to the 3 0 untranslated region of SHIP-1 was confirmed by luciferase reporter assay. Transfection of a myeloid cell line with miR-210 resulted in loss of SHIP-1 protein expression. These data suggest that miR-155 and miR-210/SHIP-1/Akt pathways could serve as clinical biomarkers for disease progression, and that miR-155 and miR-210 might serve as novel therapeutic targets in MDS.

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“…As a consequence of these wideranging activities, germ-line or B-cell-specific deletion of FcγRIIB or SHIP-1 in mice results in a severe lupus-like disease characterized by high-titer serum IgG antinuclear autoantibodies, lymphadenopathy, splenomegaly, renal failure, and increased mortality (23)(24)(25)(26)(27). MiR-155 has been reported to regulate SHIP-1 expression in mammalian myeloid and malignant B cells (28)(29)(30)(31). However, it is not known whether SHIP-1 regulation by miR-155 affects GC reactions or peripheral tolerance during a protective immune response or in an autoimmune environment, such as that in Fas lpr mice.…”

mentioning

confidence: 99%

Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in theFas^lprmouse

Thai

Patterson

Pham

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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regulates antibody responses and subsequent B-cell effector functions to exogenous antigens. However, the role of miR-155 in systemic autoimmunity is not known. Using the death receptor deficient (Fas lpr ) lupus-prone mouse, we show here that ablation of miR-155 reduced autoantibody responses accompanied by a decrease in serum IgG but not IgM anti-dsDNA antibodies and a reduction of kidney inflammation. MiR-155 deletion in Fas lpr B cells restored the reduced SH2 domain-containing inositol 5′-phosphatase 1 to normal levels. In addition, coaggregation of the Fc γ receptor IIB with the B-cell receptor in miR-155 −/− -Fas lpr B cells resulted in decreased ERK activation, proliferation, and production of switched antibodies compared with miR-155 sufficient Fas lpr B cells. Thus, by controlling the levels of SH2 domaincontaining inositol 5′-phosphatase 1, miR-155 in part maintains an activation threshold that allows B cells to respond to antigens.ERK pathways | SHIP-1 M icroRNA-155 (miR-155) plays a critical role in the generation of effective antibody responses to exogenous antigenic challenges in mice (1-3). MiR-155 levels have been reported to be elevated in B but low in T cells from patients with systemic lupus erythamosus (4), yet it is not known whether miR-155 controls autoimmune responses and the expression of related pathology.Mice harboring ubiquitous or B-cell-specific ablation of the death receptor Fas develop a severe lupus-like disease. B-cellspecific deletion of the death receptor (fas −/− ) fas −/− mice develop an excessive germinal center (GC)-derived IgG autoantibody deposition in their kidneys and succumb to renal failure (5). It has been suggested that loss of tolerance in lpr mice results from the down-regulation of the low-affinity IgG inhibitory receptor FcγRIIB (Fc γ receptor IIB), thereby rendering their B cells incapable of terminating stimulatory signals delivered by autoantigen-containing immune complexes (6-8). However, the mechanisms whereby lack of FcγRIIB engagement would lead to autoimmunity, and whether additional factors contribute to autoimmunity, are still unclear.The SH2 domain-containing inositol 5′-phosphatase 1 (SHIP-1) phosphatase acts downstream of inhibitory cell-surface receptors (9-12), including the FcγRIIB, which is essential in opposing B-cell activation signals in mice and humans (13,14). FcγRIIB inactivation has been implicated in the development of autoreactive GC B cells and plasma cells (15), as well as in the regulation of the persistence and longevity of bone marrow plasma cells (16). After coligation of the FcγRIIB with the B-cell receptor (BCR), FcγRIIB recruits SHIP-1 to the plasma membrane, where it negatively regulates cell survival, Ca 2+ -dependent effector functions, and ERK activation, thus controlling cell proliferation, anergy, and apoptosis (17-23). As a consequence of these wideranging activities, germ-line or B-cell-specific deletion of FcγRIIB or SHIP-1 in mice results in a severe lupus-like disease characterized by high-titer serum IgG antinucl...

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Onco‐miR‐155 targets SHIP1 to promote TNFα‐dependent growth of B cell lymphomas

Cited by 193 publications

References 28 publications

Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor α (TNFα) Production via Increased mRNA Half-life in Alcoholic Liver Disease

Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor α (TNFα) Production via Increased mRNA Half-life in Alcoholic Liver Disease

Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155

Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in theFas^lprmouse

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Onco‐miR‐155 targets SHIP1 to promote TNFα‐dependent growth of B cell lymphomas

Cited by 193 publications

References 28 publications

Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor α (TNFα) Production via Increased mRNA Half-life in Alcoholic Liver Disease

Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor α (TNFα) Production via Increased mRNA Half-life in Alcoholic Liver Disease

Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155

Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in theFaslprmouse

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Product

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About

Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in theFas^lprmouse