ObjectiveTo understand the molecular mechanism of ferroptosis and its research progress and future prospects in pancreatic cancer. MethodThe relevant literature on the molecular mechanism of ferroptosis and its basic and clinical application in the occurrence and development of pancreatic cancer was retrievaled and reviewed. ResultsFerroptosis was a non-apoptotic form of cell death that depended on iron aggregation, and its molecular biological features included iron ion overload, reactive oxygen species accumulation, lipid peroxidation, and so on. Ferroptosis was closely related to cell metabolism, and the imbalance of ferroptosis caused by abnormal metabolism also existed during the tumorigenesis and progression of pancreatic cancer, which in turn triggered the abnormal proliferation of pancreatic cancer cells and leaded to their progression. By regulating the key molecular signaling pathways of ferroptosis, it was expected to find new drug targets and therapeutic pathways for pancreatic cancer treatment. The results of ferroptosis-related studies so far had shown the potential for future translational research in the field of pancreatic cancer treatment. ConclusionsThe mechanism of ferroptosis is of great value in pancreatic cancer research. At present, there are still many uncharted areas in the study of ferroptosis, and the molecular mechanisms involved are still poorly understood. In the future, as the study of ferroptosis continues, it is expected to provide new ideas for pancreatic cancer treatment and discover new targets for drug development.
The morbidity and mortality of gallbladder cancer were rising. At present, there was no effective chemotherapy regimen, so it was of great practical significance to explore new therapy target. Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. In recent years, it had become a research hotspot. Many studies had been carried out on the relevant biological mechanisms such as liver cancer, breast cancer, pancreatic cancer, and other cancer. At present, there are still few studies on ferroptosis in gallbladder cancer, and its relevant mechanisms need further in-depth analysis, which opens up a new research direction for exploring the treatment of gallbladder cancer.
Immunoglobulin A nephropathy (IgAN) is an immune-mediated chronic inflammatory disease with a complex pathogenesis and diverse clinical manifestations. Currently, there is no specific treatment plan. Programmed cell death is an active and orderly way of cell death controlled by genes in the body, which maintains the homeostasis of the body and the development of organs and tissues by participating in various molecular signaling pathways. In recent years, programmed cell death has played an important regulatory role in the occurrence and development of IgAN, involving complex signaling pathways. Under pathological conditions, it may relieve kidney damage through various pathways such as reducing oxidative stress, inhibiting inflammation, and improving energy metabolism. This article provides a review of the research progress of IgAN in apoptosis, autophagy, pyroptosis, ferroptosis,and cuproptosis in order to provide new therapeutic targets for IgAN.
Objective To summarize the papers about the research status and prospects of ferroptosis in hepatocellular carcinoma (HCC) and its drug resistance in recent years in order to provide directions and ideas for the treatment of HCC. Method The relevant literatures at home and abroad in recent years about ferroptosis in HCC and its drug resistance were reviewed. Results The mechanism of ferroptosis in the development and drug resistance of HCC was complicated, involving multiple protein and molecular pathways. Ferroptosis played an important role in improving chemotherapy and sorafenib resistance, and it had a broad application prospect in HCC. Conclusions The molecular mechanism of ferroptosis in HCC and its drug resistance has not been fully elucidated. Further research on the mechanism of ferroptosis in HCC may provide new molecular therapeutic targets for HCC. Ferroptosis has a broad application prospect in the treatment of HCC.
ObjectiveTo investigate the pan-cancer expression profile, prognostic value, co-expression networks, immune regulatory roles of BRF1, and its biological functions and molecular mechanisms in esophageal squamous cell carcinoma (ESCC). MethodsIntegrated analysis of TCGA pan-cancer datasets was performed to evaluate BRF1 expression differences between tumor/normal tissues, survival correlations, co-expressed gene-enriched pathways, and immune features (immune checkpoints, cytokines, immune cell infiltration). GEO datasets were used to validate BRF1 expression in ESCC. BRF1 was knocked down using siRNA in ESCC cells, with MTT and Transwell assays assessing proliferation/migration, and Western blot analyzing proliferation- (PCNA) and migration-related proteins (Vimentin, MMP, E-Cadherin). TCGA data were analyzed to explore BRF1-ferroptosis correlations. ResultsBRF1 was significantly upregulated in over 20 cancer types. High BRF1 expression predicted poor prognosis in adrenocortical carcinoma (ACC) and prostate adenocarcinoma (PRAD). BRF1 positively regulated T cell-mediated cell death pathways in ESCA and circadian rhythm pathways in PAAD. BRF1 exhibited cancer-type-specific correlations with immune checkpoints, cytokine networks, and immune cell infiltration. In vitro, BRF1 knockdown suppressed ESCC proliferation (PCNA downregulation) and migration (Vimentin/MMP downregulation, E-Cadherin upregulation). BRF1 expression positively correlated with ferroptosis antagonists (GPX4, HSPA5, SLC7A11). ConclusionBRF1 demonstrates complex pan-cancer expression and functional heterogeneity, modulating tumor progression and immune infiltration. BRF1 promotes ESCC proliferation and migration, potentially via ferroptosis resistance regulation, highlighting its potential as a therapeutic target in ESCC.
Objective To investigate the regulatory role of PLA2G4A targeting in ferroptosis and its sensitizing effect on the ferroptosis inducer Erastin. Methods PLA2G4A expression in lung adenocarcinoma (LUAD) was assessed by analyzing data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium databases, followed by immunohistochemical validation. PLA2G4A expression was knocked down in H1299 lung cancer cells using small interfering RNA. The correlation between PLA2G4A and ferroptosis marker genes was examined through gene correlation analysis and Western blotting. The regulatory relationship between PLA2G4A and ferrous ion (Fe2+) was analyzed using high-content fluorescence imaging. Cell proliferation after PLA2G4A inhibition and Erastin treatment was measured by CCK-8 assay. Flow cytometry and high-content fluorescence imaging were employed to evaluate the effects of PLA2G4A suppression combined with Erastin on intracellular Fe2+ and lipid peroxidation levels. Results Both mRNA (P<0.05) and protein (P<0.001) levels of PLA2G4A were significantly upregulated in LUAD tissues, and its high expression was associated with poor prognosis in LUAD patients (P<0.05). PLA2G4A expression was positively correlated with SLC7A11 expression (r=0.23, P<0.001). PLA2G4A knockdown suppressed SLC7A11 protein expression and increased cellular Fe2+ levels (P<0.01). Compared with the control group, PLA2G4A-silenced cells exhibited significantly reduced viability upon Erastin treatment (P<0.001). Furthermore, Erastin enhanced PLA2G4A targeting-induced Fe2+ accumulation and lipid peroxidation (P<0.001). Conclusion Targeting PLA2G4A induces ferroptosis in lung cancer cells by inhibiting SLC7A11 expression and enhances their sensitivity to Erastin.
ObjectiveTo construct a prognostic prediction model for hepatocellular carcinoma (HCC) based on disulfidptosis-associated genes (DAGs) and ferroptosis-associated genes (FAGs) using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases and explore the immune characteristics and antitumor drug sensitivity of HCC patients with high- and low-risk score. MethodsThe transcriptomic and clinical data of HCC were downloaded from the TCGA and ICGC databases. The expression levels of DAGs and FAGs were extracted. Subsequently, the differentially expressed and prognostically relevant DAGs and FAGs (DFAGs) were screened through differential expression and prognostic analysis. A prognostic prediction model for HCC was constructed by LASSO regression analysis. The prognostic value of risk factors was evaluated using univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, receiver operating characteristic curves, principal component analysis, and t-distributed stochastic neighbor embedding. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to further elucidate the mechanisms of genes associated with HCC prognosis. The impact of risk factors on immune cells and immune cells functions was analyzed using single-sample gene set enrichment analysis. Based on the Genomics of Drug Sensitivity in Cancer database, the oncoPredict package was used to predict responses to antitumor drugs in for different risk groups. ResultsFour DFAGs (SLC7A11, SLC1A5, G6PD, and LRPPRC) with respective risk coefficients of 0.0350, 0.0442, 0.1597, and 0.0132 were selected to construct the prognostic prediction model. The risk score of prognostic prediction model was calculated as: Risk score =(0.0350×SLC7A11 expression level) + (0.0442×SLC1A5 expression level) + (0.159 7×G6PD expression level) + (0.013 2×LRPPRC expression level). The multivariate Cox regression analysis indicated that a high-risk score was an independent risk factor for HCC patient survival [HR (95%CI) = 5.414 (1.918, 15.279), P<0.001]. Both TCGA and ICGC datasets demonstrated that the high-risk patients had significantly worse survival than low-risk patients (P<0.001 and P=0.003, respectively). Enrichment analysis revealed that the risk-associated genes influenced HCC progression through multiple pathways, such as immune response, cell cycle, glycolysis, gluconeogenesis. Immune analysis showed that the high-risk patients exhibited increased infiltration of immunosuppressive cells, such as activated dendritic cells, macrophages, and regulatory T cells, while natural killer cell infiltration was significantly reduced. The drug sensitivity analysis suggested that the high-risk HCC patients might respond better to 5-fluorouracil, afatinib, cyclophosphamide, and lapatinib, whereas the low-risk patients might benefit more from oxaliplatin and sorafenib. ConclusionsHCC prognosis prediction model based on DFAGs in this study suggests a certain predictive value for the survival of HCC patients in the data from both TCGA and ICGC datasets. There are significant differences in pionts of immune cells infiltration and immune cells functions between high-risk and low-risk HCC patients. Additionally, significant differences exist in sensitivity to targeted drugs and chemotherapeutic drugs. This model can provide some references for immunotherapy, personalized treatment, and prognosis evaluation of HCC patients.
Neuropathic pain (NP) is a pathological state caused by damage or disease to the somatosensory nervous system. Programmed cell death (PCD) is an orderly process of cell death regulated by both intrinsic signals and external stimuli. In recent years, an increasing number of studies have shown that PCD plays a key regulatory role in the pathogenesis of NP. This article reviews the molecular mechanisms of various types of PCD and their specific roles in NP, in order to provide new research directions for the prevention, diagnosis, and treatment of NP.
ObjectiveTo investigate the effect of Huaier extract on the proliferation, invasion, and ferroptosis pathways of colorectal cancer (CRC) cells. MethodsThe CRC cell line SW620 was cultured in vitro, and the cells were treated with Huaier extract solution at different concentrations (0, 5, 10, 20, and 50 mg/mL). The cell counting kit 8 was used to detect the proliferation of CRC cells at different concentrations to scree the test dose of the Huaier extract. The Transwell and the scratch assays were used to detect the cell invasion and migration. The reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA) kits were used to detect the cellular oxidative stress level. The Western blot was used to detect the ferroptosis-related proteins levels, including glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (NRF2), and high mobility group box-1 (HMGB1). ResultsIn this study, it could statistically inhibit the proliferation of CRC cells after 48 h interfering with Huaier extract at 10, 20 mg/mL concentrations, so we chose 10, 20 mg/mL concentrations as the test dose, 0 mg/L as the control dose. Huaier extract effectively inhibited the migration and invasion abilities of SW620 cells in a dose-dependent manner (Transwell: F=480.0, P<0.001; scratch assay: F=24.3, P=0.001). The level of ROS in the SW620 cells increased with the increase of concentration in a dose-dependent manner (F=806.3, P<0.001). the level of GSH in the SW620 cells decreased with the increase of concentration in a dose-dependent manner (F=35.0, P=0.005), but the level of MDA was highest at 10 mg/mL (F=22.9, P=0.002) . Further the Huaier extract could effectively reduce the expressions of GPX4 (F=74.2, P<0.001), NRF2 (F=32.8, P=0.001), and HMGB1 (F=55.1, P<0.001) in a dose-dependent manner. ConclusionFrom the results of this study, Huaier extract at 10 and 20 mg/mL concentrations can inhibit the proliferation and invasion of CRC SW620 cells by inducing ferroptosis.
Objective A series of bioinformatics methods were used to identify ferroptosis related biomarkers in lupus nephritis (LN). Methods We retrieved sequencing data of GSE112943 from the GEO (Gene Expression Omnibus) database and screened LN differentially expressed genes. We searched for ferroptosis-related gene (FRG) through FerrDb database, and screened LN-FRG. We conducted enrichment analysis on the LN-FRGs using David online bioinformatics database and screened the core LN-FRG using cytoHubba. We used external data sets to verify the core LN-FRGs, constructed competing endogenous RNA networks, and conducted molecular docking analysis. Results A total of 37 LN-FRGs were selected through screening. These genes are mainly enriched in inflammation, immune regulation and ferroptosis related signaling pathways. Through the cytoHubba and external dataset validation, the key core LN-FRG of ATF3 (activating transcription factor 3) was ultimately identified, and its expression was significantly increased in LN (P<0.05). Molecular docking analysis showed that ATF3 was closely bound to SLC7A11 and NRF2, and may participate in the occurrence and development of LN through the microRNA-27-ATF3 regulation axis. Conclusion The pivotal gene ATF3 may participate in the inflammation and immune injury of LN through ferroptosis.