Overexpression of aquaporin1 plays a vital role in proliferation, apoptosis and pyroptosis in Wilms’ tumor
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PROVIDER: PRJNA1038709 | ENA |
REPOSITORIES: ENA
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Project description:Background: Nephroblastoma, also known as Wilms’ tumor (WT), is an embryonic malignant tumor and one of the most common malignant tumors in the abdominal region of children. Previous studies have demonstrated that aquaporin 1 (AQP1), a highly expressed channel protein in the kidneys, is closely associated with various diseases and also plays a significant role in tumorigenesis and progression. However, the exact role and underlying mechanisms of AQP1 in the occurrence and development of nephroblastoma remain unclear. Methods: After overexpression of AQP1, cell proliferation was assessed using the CCK-8 proliferation assay and EdU staining. Flow cytometry was employed to detect cell apoptosis, and Western blotting (WB) analysis was conducted to validate the expression of relevant protein markers. mRNA Sequencing (mRNA-Seq) was performed on WT cells with AQP1 overexpression to predict and characterize the associated mechanisms. Transmission electron microscopy was utilized to observe changes in the ultrastructure of WT cells undergoing apoptosis and pyroptosis following AQP1 overexpression. Functional in vivo validation was conducted through animal experiments. Results: We validated at both in vitro and in vivo levels that overexpression of AQP1 inhibited cell proliferation and promoted cell apoptosis and pyroptosis. mRNA-Seq analysis of WT cells with AQP1 overexpression suggested that these effects might be mediated through the inhibition of the JAK-STAT signaling pathway, which was further experimentally validated. Additionally, we discovered that overexpression of AQP1 activated the classical pyroptosis signaling pathway dependent on Caspase-1, thereby promoting pyroptosis in WT. Conclusion: These findings highlight the significant functional role of AQP1 in the pathobiology of nephroblastoma, providing novel insights into the development of this disease. Moreover, these results offer new perspectives on the potential therapeutic targeting of AQP1 as a treatment strategy for nephroblastoma.
2024-02-14 | GSE247460 | GEO
Project description:summary (1)Objective: To investigate the antileukemic role of Lip-1 in K562 leukemia cells. (2)Methods: We performed CCK-8, flow cytometry, microscopy, western blotting assay, next generation sequencing, PCR assays to evaluate the effect of Lip-1 in K562 leukemia cells. (3)Results: Lip-1 inhibited K562 cell proliferation in a dose- and time-dependent manner. RNA sequencing revealed several pathways that were affected by Lip-1, such as the G1/S transition of the mitotic cell cycle and extrinsic or intrinsic apoptotic signaling pathways. The results of flow cytometry indicated that Lip-1 arrests the cell cycle. K562 cells were characterized by swelling and plasma membrane rupture. The expression of the hallmark of pyroptosis, the cleaved N-terminal GSDME, increased. Endoplasmic reticulum stress and autophagy were involved in Lip-1-induced cell death. (4)Conclusion：Lip-1 induces cell cycle arrest, apoptosis, and secondary pyroptosis in K562 leukemia cells, which provides new hope for the treatment of leukemia.
2022-05-31 | GSE205036 | GEO
Project description:The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation. We used microarrays to explore the gene expression profiles differentially expressed in influenza-infected bone marrow derived macrophages (BMDM) isolated from Ifnar1-/- and wild-type mice.
2016-08-11 | E-GEOD-77611 | biostudies-arrayexpress
Project description:Lip-1 induces cell cycle arrest, apoptosis, and pyroptosis in K562 cells
| PRJNA843318 | ENA
Project description:Unexpected cross-talk between the pathogen defense mechanisms of apoptosis, necroptosis, and pyroptosis.
| PRJNA545997 | ENA
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:Wilms tumor (WT) is the most common renal malignancy in children. So we aim to investigate the transcriptomic map of Wilms tumor.
2022-05-18 | GSE138869 | GEO
Project description:The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that plays important roles during development of several organs including metanephric kidneys. A number of WT1 target genes have been identified, but the detailed mechanisms by which WT1 orchestrates renal development remain elusive. To identify WT1 target genes relevant to development, genome-wide expression profiling was performed using oligonucleotide microarrays representing 39,000 human transcripts Keywords: Wilms' tumor 1 (WT1) gene, -KTS isoform; time course
2007-06-21 | GSE5117 | GEO
Project description:Induction of cell death represents a primary goal of most anti-cancer treatments. Despite the efficacy of such approaches, a small population of “persisters” develop evasion strategies to therapy-induced cell death. While previous studies have identified mechanisms of resistance to apoptosis, the mechanisms by which persisters dampen other forms of cell death, such as pyroptosis, remain to be elucidated. Pyroptosis is a form of inflammatory cell death that involves formation of membrane pores, ion gradient imbalance, water inflow and membrane rupture. Herein, we investigate mechanisms by which cancer persisters resist pyroptosis, survive, then proliferate in the presence of tyrosine kinase inhibitors (TKI). Lung, prostate and esophageal cancer persister cells remaining after treatments exhibited several hallmarks indicative of pyroptosis resistance. The inflammatory attributes of persisters included chronic activation of inflammasome, STING, and type I interferons. Comprehensive metabolomic characterization uncovered that TKI-induced pyroptotic persisters display high methionine consumption and excessive taurine production. Elevated methionine flux or exogenous taurine maintained plasma membrane integrity via osmolyte-mediated effects. Increased dependency on methionine flux decreased the level of one carbon metabolism intermediate S-(5'-adenosyl)-L-homocysteine, a determinant of cell methylation capacity. The consequent increase in methylation potential induced DNA hypermethylation of genes regulating metal ion balance and intrinsic immune response. This enabled thwarting TKI resistance by using the hypomethylating agent decitabine. In summary, the evolution of resistance to pyroptosis can occur via a stepwise process of physical acclimation and epigenetic changes without existing or recurrent mutations.
2022-12-02 | GSE219044 | GEO
Project description:Biomimetic nanococrystals are prepared using the preferred combination of mitoxantrone and gambogic acid for rational drug delivery. The unique mechanism of obtained nanococrystals regulating pyroptosis genes through ribosomal stress is revealed by TMT-proteomics of 4T1 cells.
2024-07-27 | PXD053939 | Pride