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Targeting canonical and non-canonical STAT3 signaling by WB737, a novel potent STAT3 inhibitor, in natural killer/T-cell lymphoma

ABSTRACT: Targeting canonical and non-canonical STAT3 signaling by WB737, a novel potent STAT3 inhibitor, in natural killer/T-cell lymphoma

PROVIDER: PRJNA837858 | ENA |

REPOSITORIES: ENA

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Targeting canonical and non-canonical STAT3 signaling by WB737, a novel potent STAT3 inhibitor, in natural killer/T-cell lymphoma

Project description:Activating mutations of STAT3 were frequently found in patients with natural killer/T-cell lymphoma (NKTL), suggesting that targeted inhibition of STAT3 is a potential therapeutic option for NKTL patients. Here, we have developed a novel and potent STAT3 inhibitor WB737 that directly binds to the STAT3-SH2 domain with high affinity. WB737 selectively inhibits cell growth of NKTL harbored STAT3 mutations through inducing apoptosis and blocking colony formation. Mechanistically, WB737 inhibits both canonical and non-canonical STAT3 signaling via suppression of STAT3 phosphorylation at Tyr705 and Ser727 sites, respectively. Moreover, the activity of WB737 has a more potent inhibition on STAT3 compared to Sttatic, resulting in a significant anti-tumor effect followed by almost complete tumor regression in a NKTL xenograft model harboring STAT3 activating mutation. Collectively, these findings provide a preclinical proof-of-concept for WB737 as a novel therapeutic strategy for the treatment of NKTL patients with STAT3-activating mutations.

2023-06-21 | GSE202944 | GEO

Natural killer cell proliferation requires canonical IRE1 function during viral infection

Project description:Natural killer cell proliferation requires canonical IRE1 function during viral infection

| PRJNA992477 | ENA

IL-6/Stat3-Dependent Induction of Distinct, Obesity-Associated Natural Killer Cells Deteriorates Energy and Glucose Homeostasis

Project description:Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes the expansion of interleukin-6 receptor (IL6Ra)-expressing NK cells, which also express a number of other myeloid lineage genes such as the colony-stimulating-factor 1 receptor (Csf1r). Selective ablation of Csf1r- expressing NK cells prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of myeloid signature NK cells, protects from obesity, insulin resistance and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity, correlate with markers of systemic low-grade inflammation and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on IL-6/Stat3-dependent formation of distinct NK cells, which may provide a novel target for the treatment of obesity, metaflammation-associated pathologies and diabetes.

2017-07-05 | GSE99068 | GEO

Natural killer cell proliferation requires canonical IRE1 function during viral infection (CITE-Seq)

Project description:Natural killer cell proliferation requires canonical IRE1 function during viral infection (CITE-Seq)

| PRJNA992482 | ENA

Natural killer cell proliferation requires canonical IRE1 function during viral infection (RNA-Seq)

Project description:Natural killer cell proliferation requires canonical IRE1 function during viral infection (RNA-Seq)

| PRJNA992481 | ENA

Non-canonical STAT3 activity sustains pathogenic Th17 proliferation and cytokine response to antigen

Project description:Non-canonical STAT3 activity sustains pathogenic Th17 proliferation and cytokine response to antigen

2020-07-01 | GSE151447 | GEO

Expression profiling of Natural killer B cells

Project description:Investigation of global gene expression levels between B cells, Natural killer cells and Natural killer B cells Gene expression profiling using sorted B cells, Natural killer cells and Natural killer B cells from WT mouse spleen. Total RNA extracted from WT cells were quantified by the NanoDrop ND-1000 and RNA integrity was assessed by standard denaturing agarose gel electrophoresis. The sample preparation and microarray hybridization were performed based on the NimbleGenâs standard protocols.

2016-05-17 | E-GEOD-80063 | biostudies-arrayexpress

miRNA expression profiling of NKTCL (Natural Killer/T-Cell Lymphoma) samples

Project description:We performed a comprehensive genome-wide miRNA expression profiling (MEP) of extranodal nasal-type Natural Killer/T-cell lymphoma (NKTL) using formalin fixed paraffin-embedded tissue (FFPE) (n=30) and NK cell lines (n=6) in comparison with normal NK cells, with the objective of understanding the pathogenetic role of miRNA deregulation in NKTL. Total RNA, including miRNA, were extracted using Ambion Recoverall Kit and profiled using Agilent human miRNA V2.

2011-11-23 | E-GEOD-31377 | biostudies-arrayexpress

miRNA expression profiling of NKTCL (Natural Killer/T-Cell Lymphoma) samples

2011-11-23 | GSE31377 | GEO

Transcription profiling of neonatal and adult mouse natural killer cells

Project description:Comparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.

2005-10-01 | E-MEXP-354 | biostudies-arrayexpress

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