Nur77 induces GSDMC-mediated pyroptosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1141494 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pyroptosis is a type of lytic cell death executed by members of the gasdermin family. It has been demonstrated that induction of pyroptosis can effectively inhibit tumor growth, which implicates a new strategy for clinical tumor therapy, especially for those tumors (such as melanoma) that are insensitive or resistant to the induction of apoptosis.By means of a chemical compound DBIC, designed and identified by our group recently, to induce GSDMC-mediated pyroptosis in melanoma cells.
2025-07-07 | GSE273365 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic and lethal disease. Gasdermins are primarily associated with necrosis via membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. In this study, we report GSDMC upregulation during PDAC progression. GSDMC directly induces genes related to stemness, EMT, and immune evasion. Targeting Gsdmc in murine PDAC models reprograms the immunosupressive tumor microenvironment, resulting in diminished tumor initiation, growth, metastasis, and enhanced response to PD-1 checkpoint inhibition. Mechanistically, we discover that ADAM17 cleaves GSDMC, releasing a C-terminal fragment that translocates to the nucleus and binds to promoter regions of stemness, metastasis, and immune evasion-related genes. Pharmacological inhibition of GSDMC cleavage or hindrance of its nuclear translocation was equally effective in suppressing downstream targets and inhibiting PDAC progression. Our findings position GSDMC as a potential therapeutic target for enhancing treatment response in this deadly disease.
2024-09-18 | GSE243462 | GEO
Project description:Pyroptosis is a recently discovered form of lytic cell death that is characterized by cell swelling and formation of pores and large bubbles on the plasma membrane. We find radiation could induce pyroptosis in human colorectal cancer HCT116 cells, and irradiation induces pyroptosis in mouse normal intestine MODEK cells only after 36 hours and over 8.0 Gy. In view of the significant pyroptosis effect of MODE-K cells, we selected 4Gy and 12Gy, 24h and 48h for experiments. After ONT full-length transcriptome sequencing, the cell pyroptosis model can screen out the differential genes related to cell pyroptosis, which is helpful to further explore the mechanism of pyroptosis of MODE-K cells.
2024-08-01 | GSE211709 | GEO
Project description:We identified that Gsdmc gene is important for pancreatic cancer in tumorigenesis and metastasis. Here we used KPC mice (LSL-KrasG12D/+; p53f/f; Pdx1-Cre)-derived cancer cells, KPC cells in short, to check the effects of Gsdmc knockdown on primary tumor growth and metastasis. The results suggested that Gsdmc knockdown inhibited the expression of key genes in multiple pathways, including cell migration, epithelial-mesenchymal transition, immune cell recruitment, and so on. The data deposited here provides the transcriptomic alteration of KPC cells after Gsdmc knockdown with two shRNAs.
2024-09-18 | GSE250062 | GEO
Project description:We isolated total RNA from gastrocnemius muscle of wildtype and muscle-specific Nur77 overexpressing transgenic mice to identify Nur77-mediated changes in gene expression. Findings confirmed changes in genes involved in carbohydrate metabolism and muscle development.
2015-02-04 | GSE65585 | GEO
Project description:We isolated total RNA from gastrocnemius muscle of wildtype and muscle-specific Nur77 overexpressing transgenic mice to identify Nur77-mediated changes in gene expression. Findings confirmed changes in genes involved in carbohydrate metabolism and muscle development. 2 replicate Illumina Single Color Mouse WG-6_V2_0 chips were used. 6 wildtype and 6 transgenic mice overexpressing Nur77 in skeletal muscle were used. RNA was isolated by Trizol and further purified through RNEasy column. RNA from 2 mice were pooled, for a total of 6 samples -- 3 wildtype and 3 transgenic. The same samples were split into two technical replicate chips. Each chip contains 3 wildtype and 3 transgenic samples.
2015-02-04 | E-GEOD-65585 | biostudies-arrayexpress
Project description:Tissue damage and repair are hallmarks of inflammation. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on how inflammation affects repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa. We found that type III, not type I or II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed following intestinal damage are sensed by ZBP1, leading to Caspase-8 activation, and cleavage of Gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays repair of the large or small intestine after colitis or irradiation, respectively. The type III interferon/ZBP1/Caspase-8/GSDMC axis is also active in patients with inflammatory bowel disease (IBD). Our findings highlight the capacity of type III interferons to delay gut repair, which has important implications for IBD patients or individuals exposed to radiation therapies.
2024-11-01 | GSE277150 | GEO
Project description:Tissue damage and repair are hallmarks of the inflammatory process. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on how inflammatory mediators affect repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa driven by inflammation or genotoxicity. We found that type III, but not type I or II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed during the damage and repair process are then sensed by ZBP-1, leading to Caspase-8 activation, and cleavage of Gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays the re-epithelialization of the large or small intestine after colitis or irradiation, respectively. We also found that the type III interferon/ZBP1/Caspase-8/GSDMC pathway is activated in patients with inflammatory bowel disease (IBD). Our findings highlight a molecular signaling cascade initiated by type III interferons that delays intestinal tissue repair, which has important implications for IBD patients or individuals exposed to radiation therapies.
2024-11-01 | GSE276837 | GEO
Project description:Regulation of pyroptosis in radiation induces mouse intestine cells
| PRJNA871879 | ENA
Project description:Mst1-mediated phosphorylation of Nur77 is required for embryo implantation
| PRJNA816101 | ENA