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 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.
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.
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.
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.
ObjectiveTo summarize the mechanism and research progress of ferroptosis in acute liver injury. MethodThe domestic and foreign literatures related of ferroptosis and acute liver injury were searched and reviewed. ResultsFerroptosis was a newly identified form of iron-dependent cell death. The loss of lipid peroxidation repair activity of glutathione peroxidase 4, the presence of redox active iron and the oxidation of phospholipids containing polyunsaturated fatty acids were considered to be distinctive features of ferroptosis. At present, the research on the regulation of ferroptosis genes involved common liver diseases, including drug-induced liver injury, hepatocellular carcinoma, liver fibrosis, liver ischemia-reperfusion injury, liver failure, nonalcoholic fatty liver and so on. Based on the high correlation between ferroptosis and acute liver injury, chemical therapy targeting ferroptosis could provide individualized treatment for patients with acute liver injury in the future. ConclusionsThe ferroptosis plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of acute liver injury through diverse mechanisms. Thoroughly exploring the involvement of the ferroptosis in acute liver injury is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of acute liver injury.
ObjectiveTo summarize a comprehensive overview of the mechanism of ferroptosis and its associated microRNAs in the occurrence and development of hepatocellular carcinoma (HCC), and to offer novel insights and potential avenues for tumor marker screening and targeted treatment in clinical hepatocellular carcinoma patients. MethodThe literatures on the basic and clinical application research of ferroptosis and related microRNA in the occurrence, development and prognosis of HCC at home and abroad in recent years were reviewed and summarized, and the research progress of microRNA regulating ferroptosis in HCC was summarized. ResultsMicroRNA, a type of non-coding small RNA, had the ability to regulate gene expression at the post-transcriptional and translational levels. It held promising potential in the diagnosis and treatment of HCC. Ferroptosis, on the other hand, was a form of cell death triggered by iron-dependent lipid peroxidation. It played a crucial role in the development of HCC. A series of miRNAs related to ferroptosis might act as HCC growth regulators to regulate the growth of cancer cells, or reverse the drug resistance of cancer cells, thereby promoting or inhibiting the occurrence and progression of HCC. ConclusionsMicroRNA can regulate the occurrence and development of HCC through the ferroptosis pathway and may become tumor markers for the early diagnosis of HCC. Additionally, microRNA may also serve as a related therapeutic target and provide a new treatment option for HCC.
ObjectiveTo establish and validate the diagnostic model of ferroptosis genes for acute myocardial infarction (AMI) based on bioinformatics. MethodsFive AMI gene expression data were obtained from Gene Expression Omnibus (GEO), namely GSE66360, GSE48060, GSE60993, GSE83500, GSE34198. Among them, GSE66360 was used as the training set to perform differential analysis, and intersection of differential genes and ferroptosis genes was taken to obtain differentially expressed ferroptosis genes in AMI. GO and KEGG enrichment analysis was performed using Metascape website. Subsequently, random forest (RF) algorithm was used to screen out key genes with high classification performance according to the Keeny coefficient score, and artificial neural network (ANN) diagnostic model of AMI ferroptosis feature gene was constructed by model group GSE83500. The area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation was used to evaluate the performance and generalization ability of the model, and 3 external independent datasets were used to verify the diagnostic performance of this model. The single sample gene setenrichment analysis was used to explore the difference in immune cell infiltration between infarcted myocardium and normal myocardium after AMI. In addition, correlation analysis between immune cells and key genes was also conducted. Finally, potential drugs that would prevent and treat AMI by regulating ferroptosis were screened out from the Coremin Medical platform. ResultsA total of 16 differentially expressed ferroptosis genes were obtained in the training set, GO enrichment analysis showed that they mainly participated in biological functions such as cellular response to biological stimuli and chemical stress, regulation of interleukin 17, etc. KEGG enrichment analysis showed that these genes were significantly enriched in NOD-like receptor signaling pathway, programmed cell necrosis, Leishmaniasis and other pathways. Four genes with good classification performance were screened out using RF algorithm, namely EPAS1, SLC7A5, FTH1, and ZFP36. The results of 10-fold cross-validation showed that the minimum AUC value was 0.746, the maximum value was 0.906, and the average value was 0.805. The AUC of the ANN model was 0.859, and the AUC values of the three independent validation sets were 0.763 (GSE48060), 0.673 (GSE60993), 0.698 (GSE34198). Immune cell infiltration found that macrophages, mast cells and monocytes were significantly active after AMI. Correlation analysis found that there were positive correlations between 4 key genes and activated dendritic cells, eosinophils and γδT cells. A total of 20 potential western medicines were predicted which could prevent and treat AMI by regulating ferroptosis, and the predicted potential Chinese medicine was mainly heat-clearing and detoxifying and blood-activating and removing blood stasis drugs. ConclusionThe identified AMI ferroptosis genes by bioinformatics method have certain diagnostic significance, which provides a reference for disease diagnosis and treatment.
Objective To observe the expression of hepcidin-ferroportin (FPN) pathway in adenine-induced chronic kidney disease (CKD) rat model and to explore the mechanism of its involvement in renal fibrosis in CKD. Methods A total of 20 6-week-old male SD rats without specific pathogen were selected. The rats were divided into control group and CKD group, with 10 rats in each group, using a simple random method. Rats were sacrificed at the end of the second and sixth weeks after modeling. The levels of serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urine protein quantification were measured. The pathological changes of rats were observed. The iron content of rat kidney tissue was detected by colorimetric method, and the level of serum hepcidin-25 was detected by enzyme linked immunosorbent assay method in both groups. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to detect the renal protein and mRNA expression of α-smooth muscle actin (α-SMA), collagen type Ⅰ (Col-Ⅰ), FPN1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) P65. Results Compared with the control group, the levels of Scr, BUN, and 24 h urine protein quantification were higher in the CKD group at the end of the second and sixth weeks of modeling (P<0.05). The results of renal tissue staining showed that the CKD group had obvious glomerular structural disorders, tubular dilation, and interstitial collagen fiber deposition. Compared with the control group, the serum hepcidin-25 level and the iron content of kidney tissues in the CKD group were significantly higher, and correlation analysis suggested that both were positively correlated with the renal function of rats (P<0.05). Compared with the control group, the protein and mRNA expression levels of α-SMA, Col-Ⅰ, HAMP, IL-6, TNF-α, NF-κB P65 were higher (P<0.05), while FPN1 expression was lower in CKD group at the end of the second and sixth weeks of modeling (P<0.05). Correlation analysis results showed that HAMP mRNA expression was positively correlated with α-SMA, Col-Ⅰ, IL-6, TNF-α, and NF-κB p65 (P<0.001), which was negatively correlated with FPN1 mRNA expression (P<0.001). FPN1 mRNA expression was significantly negatively correlated with α-SMA, Col-Ⅰ (P<0.001). Conclusions Ferroptosis may be present in the adenine-induced rat model of CKD, and it may be involved in the process of renal fibrosis through the interaction of HAMP-FPN signaling pathway with the inflammatory response. Serum hepcidin-25 is expected to be a serological marker for the early diagnosis of CKD.