The differentially expressed genes after overexpression of NINJ1 in gastric cancer cell lines
Ontology highlight
ABSTRACT: This study aimed to explore the underlying molecular mechanism of NINJ1 in gastric cancer progression. NINJ1 acts as ferroptosis suppressor by inactivation of AKR1C1/CYP1B1 axis.
Project description:Ferroptosis is a regulated form of necrotic cell death caused by an iron-dependent accumulation of oxidized phospholipids in cellular membranes, which culminates in plasma membrane rupture (PMR) and cell lysis. PMR is also a hallmark of other types of programmed necrosis, such as pyroptosis and necroptosis, where it is initiated by dedicated pore-forming cell death executors. Yet, whether ferroptosis-associated PMR is actively executed by a protein or driven by osmotic pressure remains unknown. Here, we investigated the role of ninjurin-1 (NINJ1), the recently identified executor of pyroptosis-associated PMR, in ferroptosis. We report that during ferroptosis NINJ1 oligomerizes and that Ninj1-deficiency protects macrophages and fibroblasts from ferroptosis-associated PMR. Mechanistically, we find that NINJ1 is dispensable for the early steps of ferroptosis, such as lipid peroxidation, channel-mediated calcium influx and cell swelling. By contrast, NINJ1 is required for early loss of plasma membrane integrity, an event that precedes complete PMR. Furthermore, NINJ1 mediates the release of cytosolic proteins and danger-associated molecular patterns (DAMPs) from ferroptotic cells, suggesting that targeting NINJ1 could be a therapeutic option to reduce ferroptosis-associated inflammation.
Project description:We have identified mouse Ninj1 as a protein responsible for plasma membrane integrity following cell death stimuli. Ninj1 KO BMDMs have a distinct bubble morphology wherein cell cytoplasmic contents fail to be released following cell death. To determine contributing factors to Ninj1 KO morphology, we performed RNAseq in WT and Ninj1 KO murine BMDMs with or without priming.
Project description:We have applied bulk RNA sequencing as an unbiased transcriptomics to explore the association between Ninj1 deletion and macrophage activation.
Project description:In this study, we used miRNA sequencing to analyze and identify possible miRNAs that can be regulated by and UBE2CP3 in gastric cancer. The results showed that lncRNA UBE2CP3 overexpression decreased the expression of miR-138-5p. Due to miR-138-5p was able to target ITGA2 expression, and UBE2CP3 knockdown significantly downregulates ITGA2 expression, we speculated UBE2CP3 may positively regulate ITGA2 expression through sponging miR-138-5p in GC.
Project description:To identify the differentially expressed genes in normal gastric mucosa and gastric cancer tissues, we employed the microarray profiling analysis. Genes with greater than 2-fold change and P-value <0.05 were identified as differentially expressed genes. From this dataset, we obtained differentially expressed genes by cluster analysis and enriched GOs was identified by Gene set enrichment analysis (GSEA) analysis, microtubule GO was one of the most enriched GOs, and the gene KIF14 was selected to go on to the next step in the study.
Project description:Innate immunity provides the first line of defense through key mechanisms, including pyrogen and cytokine production and cell death. While elevated body temperature during infection is beneficial, heat stress (HS) can lead to inflammation and pathology. Links between HS, cytokine release, and inflammation have been observed, but fundamental innate immune mechanisms driving pathology during HS remain unclear. Here, we use diverse genetic approaches to elucidate innate immune pathways in HS. Our results show that bacteria and LPS robustly increase inflammatory cell death, PANoptosis, during HS. NINJ1 is the key executioner of this cell death to release inflammatory molecules, independent of other pore-forming executioners. In an in vivo HS model, mortality is reduced by deleting NINJ1 and fully rescued by deleting key PANoptosis molecules. Our findings suggest that therapeutic strategies blocking NINJ1 or its upstream regulators to prevent PANoptosis may reduce the release of inflammatory mediators and benefit patients experiencing HS.
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide. We compared transcriptomic profiles of gastric cancer with different ferroptosis-related-scores to identify the prognostic significance of ferroptosis-related-score in gastric cancer.
Project description:Long non-coding RNAs (lncRNAs) may contribute to tumorigenesis and cancer progression by regulating the gene in various cancers, including advanced gastric cancer (AGC). To investigate differentially expressed lncRNAs in AGC, we use whole transcriptome sequencing in 3 pairs of human gastric adenocarcinoma and the corresponding normal tissues.