Interaction of IRF9 and STAT2 synergistically up-regulates IFN and PKR transcription in Ctenopharyngodon idella

Wu, Zaohe; Wang, Liqiang; Xu, Xiaowen; Lin, Gang; Mao, Huiling; Ran, Xiaoqin; Zhang, Tao; Huang, Keyi; Wang, Haizhou; Huang, Qingli; Xu, Qun; Hu, Chengyu

doi:10.1016/j.molimm.2017.03.013

Cited by 19 publications

(5 citation statements)

References 39 publications

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“…42 As for IRF9, termed as an integral transcription factor in mediating the type I interferon response, which could interacted with STAT2 and synergistically upregulated the transcriptional level of IFN and ISG genes. 43,44 With the respect of their potential role in tumor malignancy, there were many experimental and clinical evidences supporting our observations that SOCS3 and ISG20 were risky genes, while IRF9 and NLRC5 were protective genes. For instance, Feng Y reported that promoter hypermethylation of SOCS3 was a favorable prognosticator for GBM patients.…”

Section: Discussionsupporting

confidence: 81%

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

et al. 2019

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Background: Interferon treatment, as an important approach of anti-tumor immunotherapy, has been implemented in multiple clinical trials of glioma. However, only a small number of gliomas benefit from it. Therefore, it is necessary to investigate the clinical role of interferons and to establish robust biomarkers to facilitate its application. Materials and methods: This study reviewed 1,241 glioblastoma (GBM) and 1,068 lower grade glioma (LGG) patients from six glioma cohorts. The transcription matrix and clinical information were analyzed using R software, GraphPad Prism 7 and Medcalc, etc. Immunohistochemical (IHC) staining were performed for validation in protein level. Results: Interferon signaling was significantly enhanced in GBM. An interferon signature was developed based on five interferon genes with prognostic significance, which could reflect various interferon statuses. Survival analysis showed the signature could serve as an unfavorable prognostic factor independently. We also established a nomogram model integrating the risk signature into traditional prognostic factors, which increased the validity of survival prediction. Moreover, high-risk group conferred resistance to chemotherapy and high IFNB1 expression levels. Functional analysis showed that the high-risk group was associated with overloaded immune response. Microenvironment analysis and IHC staining found that high-risk group occupied a disorganized microenvironment which was characterized by an enrichment of M0 macrophages and neutrophils, but less infiltration of activated nature killing (NK) cells and M1 type macrophages. Conclusion: This interferon signature was an independent indicator for unfavorable prognosis and showed great potential for screening out patients who will benefit from chemotherapy and interferon treatment.

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Section: Discussionsupporting

confidence: 81%

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

et al. 2019

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“…Our results indicated that the decrement in RCN1 level in HEK293T/17 cells did not impact cell viability or activate ISG expression. Those results corroborate previous findings that established the incapacity of HEK293T/17 cells to activate IFN-1 signaling due to the absence of STAT2 and IRF9 genes [80]. This may be the reason why the downregulation of RCN1 does not affect the viability of the HEK293T/ 17.…”

Section: Discussionsupporting

confidence: 92%

Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

Deng,

Pan,

et al. 2023

Molecular Oncology

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Reticulocalbin‐1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN‐1) expression and promotes AML cell pyroptosis through caspase‐1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy.

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“…CRK belongs to Src homology-2 (SH2) and SH3 domain comprised of proteins that controls the coordinated combination of signaling complexes (Sriram et al, 2015 ). IRF9 is a crucial factor in the JAK/STAT signaling pathway that stimulates the antiproliferative function of IFN-α (Wu et al, 2017 ; Tsuno et al, 2009 ). A previous study found that both type I and type II OSMR activated JAK1, JAK2, and TYK2 receptor-associated tyrosine kinases (Auguste et al, 1997 ).…”

Section: Discussionmentioning

confidence: 99%

OSMR gene effect on the pathogenesis of chronic autoimmune Urticaria via the JAK/STAT3 pathway

Luo

Yang

et al. 2018

Mol Med

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BackgroundChronic autoimmune urticaria (CAU) is a common skin disease and remains unclear understanding of pathogenesis in the vast majority of cases. In order to explore a new therapy for CAU, the current study was performed to investigate the possible functioning of the Oncostatin M receptor (OSMR) gene in the autoimmunity of CAU via regulation of the JAK/STAT3 signaling pathway.MethodsCAU skin tissues from 24 CAU patients and normal skin tissues from normal subjects were collected. Hematoxylin-eosin (HE) staining was conducted to count eosinophils, and immunohistochemistry was carried out to detect the positive rate of OSMR expression in two kinds of skin tissues. A total of 72 Kunming (KM) mice were selected, and 60 mice were used for establishing CAU models and later transfected with different plasmids. The expression of inflammatory factors was evaluated by enzyme-linked immunosorbent assays (ELISA). Expressions of janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), interferon-stimulated gene 15 (ISG15), CT10-regulated kinase (CRK), and interferon regulatory factor 9 (IRF9) were identified using Western blot assay and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Epithelial cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, and cell cycle distribution and cell apoptosis were assessed using flow cytometry.ResultsThe findings confirm that OSMR protein expression and histamine release rate are highly elevated in human CAU skin tissues, and the expression of the JAK/STAT3 signaling pathway-related genes (OSMR, JAK2, STAT3, ISG15, CRK and IRF9) was up-regulated. OSMR gene silencing in CAU mice significantly decreases the content of inflammatory factors (IL-1, IL-6, IFN-γ, and IgE), the number of eosinophils, and reduces the expression of the JAK/STAT3 signaling pathway related genes, and further enhances cell proliferation, promotes cell cycle entry and inhibits apoptosis of epithelial cells.ConclusionAll aforementioned results indicate that OSMR gene silencing inhibits the activation of the JAK/STAT3 signaling pathway, thereby suppressing the development of CAU.

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Interaction of IRF9 and STAT2 synergistically up-regulates IFN and PKR transcription in Ctenopharyngodon idella

Cited by 19 publications

References 39 publications

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

OSMR gene effect on the pathogenesis of chronic autoimmune Urticaria via the JAK/STAT3 pathway

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