Gene expression profiling identifies ferroptosis-related genes in human colon cancer cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE299397 | GEO | 2026/02/11
REPOSITORIES: GEO
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Project description:To seek ferroptosis related genes in liver cancer cells, we treated HepG2 cells using ferroptosis inducer Erastin and inhibitor Ferrostatin, respectively. We found that a subset of genes were up-regulated in Erastin treatment groups and down-regulated in Ferrostatin treatment groups, suggesting that these genes might be correlated with ferroptosis.
2019-06-10 | GSE104462 | GEO
Project description:To investigate whether Akkermansia muciniphila (AKK) bacteria affects colitis by regulating the ferroptosis signaling pathway, an mouse model of colitis was constructed, and the mice were administered with AKK and the ferroptosis agonist Erastin. HE staining and transmission electron microscopy were used to observe the pathological and microstructural changes of mouse colon tissues. The number of goblet cells was examined using alcian blue staining. The expression levels of oxidative stress-related indicators and ferroptosis-related proteins were detected by ELISA, western blot and immunohistochemisty analyses. Transcriptome and non-targeted metabolome sequencing were carried out to screen for differentially expressed genes and metabolites. Immunofluorescence double staining was used to detect the co-localization of cell adhesion-related indicators.16S microbiota sequencing was performed on mouse feces. Erastin caused damage to colon tissues, decreased the expression of ZO-1 and E-Cadherin, and increased the expression of oxidative stress and ferroptosis-related indicators. The species-abundance was increased after AKK treatment, while it was decreased after treatment with AKK bacteria+Erastin. AKK alleviated inflammatory cell infiltration, reduced organelle damage, and decreased the number of goblet cells in mice with colitis. MDA, ROS, and Fe2+ levels in colitis tissues were increased, but they were decreased after AKK bacteria treatment. The expression of GPX4 and SLC7A11 was decreased, while ACSL4 was increased. After intervention with AKK bacteria, the trend of changes in the above indicators was reversed, and 19 differential pathways were enriched. In conclusion, AKK bacteria can treat colitis in mice, and its mechanism may be related to regulating the ferroptosis signaling pathway.
2025-09-23 | GSE308591 | GEO
Project description:Erastin is a small molecular compound which inhibits the system Xc- and prevents the import of cystine, reducing glutathione (GSH) biosynthesis and glutathione peroxidase 4 (GPX4) activity, and finally inducing cell death via ferroptosis. To establish a model of Erastin induced ferroptosis in glioma cells, U87 cells were treated of Erastin (10 μM, 72 h). Combination analysis of HiChIP, ChIP-seq and RNA-seq data suggests that change of chromatin loops mediated by 3D chromatin structure regulate gene expressions in glioma ferroptosis. Genes that regulated by 3D chromatin structure include genes that were reported function in ferroptosis like MDM2 and TXRND1. We propose a new regulatory mechanism governing glioma cell ferroptosis by 3D chromatin structure.
2023-10-23 | GSE236253 | GEO
Project description:Ferroptotic cell death is dependent on unrestricted lipid peroxidation rather than activation of apoptotic effector caspases. A large number of ferroptosis activators have been reported recently. We used gene sequencing to analyze the effects of four ferroptosis activators (RSL3, N6F11, Fin56 and Erastin) on global gene expression in human PDAC1 cell line.
2023-10-18 | E-MTAB-12241 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, with increasing incidence and mortality rates. Resistance to cell death is a hallmark of cancer, and ferroptosis, a form of non-apoptotic cell death, has emerged as a critical factor in tumor suppression. The RNA-binding protein IGF2BP3, which plays a significant role in colon cancer progression, has been shown to modulate various oncogenic processes. However, its involvement in ferroptosis regulation in colon cancer remains largely unexplored. This study investigates the role of IGF2BP3 in ferroptosis regulation and its potential as a therapeutic target in colon cancer. Our data show that IGF2BP3 is upregulated in colon cancer tissues and correlates with poor prognosis. Knockdown of IGF2BP3 in colon cancer cell lines enhances sensitivity to ferroptosis induction, evidenced by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, which are reversed by the ferroptosis inhibitor ferrostatin-1. Mechanistically, IGF2BP3 regulates ferroptosis by stabilizing SLC7A11 mRNA, a key ferroptosis regulator, through its interaction with the mRNA. Additionally, miR-98-5p directly targets IGF2BP3, enhancing ferroptosis sensitivity. In vivo studies confirm that IGF2BP3 knockdown suppresses tumor growth, highlighting its potential as a therapeutic target. Overall, our findings suggest that IGF2BP3 plays a pivotal role in regulating ferroptosis in colon cancer, offering new avenues for therapeutic strategies in colon cancer treatment.
2025-02-21 | GSE289758 | GEO
Project description:This report provides data on ferroptosis induced proteomic response in immortalized mouse embryonic fibroblasts which are 4-OH-TAM-inducible Gpx4−/− (referred to as Pfa1 cells). Pfa1 cells are a valuable, widespread and well characterized model for ferroptosis research. In the first part of this batch, we used Erastin to induce ferroptosis and collected samples at 0h, 24h and 48h after treatment. Untreated cells were used as a control. In the second part, we tested Liproxtatin-1 ferroptosis inhibitor on Tamoxifen-induced Pfa1 cells after 0h, 24h, 48h. Tamoxifen-induced ferroptosis activation of these cells are in PRIDE PXD040094. Pfa1 cells (a kind gift from Marcus Conrad, Munich) were cultured in RPMI-1640 media (2 g/L glucose, 10% FBS, 2 mM Gibco GlutaMAX Supplement, 1% pen/strep) at 37C with 5% CO2 in a humidified incubator. Cells (300k) were seeded on Corning 100 mm tissue-culture treated culture dishes and incubated overnight. On the next day Pfa1 cells were treated with or without 0.5 µM erastin (E7781, Sigma-Aldrich). For experiment on ferroptosis inhibition Pfa1 cells were treated with or without 1 µM Tamoxifen and 0.5 µM Liproxtatin-1 simultaneously.
2023-07-11 | PXD041463 | Pride
Project description:High-risk neuroblastoma (NB) often relapses and becomes refractory to treatment, making it a significant contributor to childhood cancer mortality despite its relative rarity. Addressing the challenges posed by NB’s resistance to conventional apoptosis-inducing therapies (e.g., chemotherapy and radiation) has become a pressing concern in pediatric oncology research. In recent years, the growing comprehension of alternative cell death modalities distinct from apoptosis has revealed a promising avenue in the endeavor to combat treatment-resistant cancers. One such mechanism, ferroptosis, has attracted increasing attention for its potential role in combating therapy-resistant cancer cells. High-risk NB typically exhibits an immune-excluded phenotype, characterized by minimal immune cell infiltration. Despite this characteristic, the mechanisms underlying immune exclusion and impaired immune activation in NB remain unclear. Here, we demonstrate that the induction of ferroptosis using Erastin, a cysteine-glutamate antiporter inhibitor, reduces NB cell proliferation and foci formation. Furthermore, our transcriptomics analysis revealed that treatment with Erastin in NB cells led to increased expression of ULBP1, a ligand to the activating natural killer (NK) cell receptor, NKG2D. Upon ferroptosis induction, the transcription factor ATF4 was found to drive ULBP1 expression in NB cells. Consistent with this, pre-treatment with Erastin sensitized NB cells to NK cell cytotoxicity in co-culture experiments. These results suggest the NK cell’s cytotoxic function can be enhanced with Erastin-mediated ferroptosis, which may be beneficial for NB patients.
2026-02-12 | GSE317656 | GEO
Project description:Background/Objectives: Ferroptosis, an iron-dependent form of cell death, shows promise as a target for therapy-resistant cancers that exhibit increased iron metabolism. Ferroptosis is primarily characterised by lipid peroxidation within cell membranes. However, many cancers evade ferroptosis by upregulation of specialised ferroptosis defence mechanisms. This study investigates ferroptosis susceptibility in Tuberous Sclerosis Complex (TSC) cell models, and ovarian and breast cancer cell lines to identify ferroptosis resistance mechanisms and therapeutic targets. Methods: We assessed ferroptosis susceptibility using the ferroptosis inducers, RSL3 and erastin. We explored ferroptosis resistance genes using inhibitors of NRF2 (ML385) and FSP1 (iFSP1). RNA-sequencing was conducted to identify dysregulated ferroptosis resistance genes and to better characterise NRF2 target genes. RNA sequencing was also performed to identify gene expression after treatment with pro-ferroptotic iron-oxide nanoparticles. Results: TSC2-deficient cells exhibited resistance to RSL3 and erastin-induced ferroptosis, which correlated with increased ferroptosis defence gene expression, including NRF2 and downstream targets. NRF2 inhibition re-sensitised TSC2-deficient cells to ferroptosis, confirming its protective role. However, FSP1 inhibition did not re-sensitise TSC2-deficient angiomyolipoma kidney tumor cells to RSL3. In contrast, FSP1 knockdown significantly enhanced ferroptosis sensitivity in ovarian (PEO1, PEO4, OVCAR3) and breast (MDA-MB-436) cancer cell lines. Notably, in MDA-MB-436 cells, FSP1 knockdown was more effective than NRF2 inhibition in reversing ferroptosis resistance. Conclusions: Our findings highlight NRF2 and FSP1 as key regulators of ferroptosis resistance in TSC2-deficient and cancer cells. However, the differential efficacy of targeting these pathways suggests that patient stratification may be necessary for optimal therapeutic strategies. Targeting NRF2 and FSP1 could enhance ferroptosis susceptibility, offering a potential therapeutic approach for ferroptosis resistance cancers.
2025-07-14 | GSE300960 | GEO
Project description:While the importance of the iron-load of lipocalin-2 (Lcn-2) in promoting tumor progression is widely appreciated, underlying molecular mechanisms largely remain elusive. Considering its role as an iron-transporter, we aimed at clarifying iron-loaded, holo-Lcn-2 (hLcn-2)-dependent signaling pathways in affecting renal cancer cell viability. Applying RNA sequencing analysis in renal CAKI1 tumor cells to explore highly upregulated molecular signatures in response to hLcn-2, we identified a cluster of genes (SLC7A11, GCLM, GLS), which are implicated in regulating ferroptosis. Indeed, hLcn-2-stimulated cells are protected from erastin-induced ferroptosis. We also noticed a rapid increase in reactive oxygen species (ROS) with subsequent activation of the antioxidant Nrf2 pathway. However, knocking down Nrf2 by siRNA was not sufficient to induce erastin-dependent ferroptotic cell death in hLcn-2-stimulated tumor cells. In contrast, preventing oxidative stress through N-acetyl-L-cysteine (NAC) supple-mentation was still able to induce erastin-dependent ferroptotic cell death in hLcn-2-stimulated tumor cells. Besides an oxidative stress response, we noticed activation of the integrated stress response (ISR), shown by enhanced phosphorylation of eIF-2α and induction of ATF4 after hLcn-2 addition. ATF4 knockdown as well as inhibition of the ISR sensitized hLcn-2-treated renal tumor cells to ferroptosis, thus linking the ISR to pro-tumor characteristics of hLcn-2. Our study provides mechanistic details to better understand tumor pro-survival pathways initi-ated by iron-loaded Lcn-2.
2021-06-02 | GSE171939 | GEO
Project description:Ferroptosis is a form of regulated cell death driven by the iron-dependent accumulation of oxidized polyunsaturated-fatty-acid-containing phospholipids (PUFA-PLs). Three key molecular features of ferroptosis are peroxidation of PUFA-PLs, accumulation of redox-active ferrous iron, and defective lipid peroxide repair (Dixon and Stockwell, 2019). However, there is currently no reliable way to selectively stain ferroptotic cells in tissue sections to characterize the extent of ferroptosis in animal models of disease and in patient tissue samples. We sought to address this gap by immunizing mice with membranes from lymphoma cells treated with the ferroptosis inducer piperazine erastin (PE), and screening ~4,750 of the resulting monoclonal antibodies generated for their ability to selectively detect cells undergoing ferroptosis. We found that one antibody, termed 3F3 Ferroptotic Membrane Antibody (3F3-FMA), was effective as a selective ferroptosis-staining reagent using immunofluorescence (IF). The antigen of 3F3-FMA was identified by immunoprecipitation and mass spectrometry as the human transferrin receptor 1 protein (TfR1), which imports iron from the extracellular environment into cells. We validated this finding with several additional anti-TfR1 antibodies, and compared them to other potential ferroptosis-detecting reagents via immunofluorescence staining, using fluorescence microscopy and flow cytometry. We found that anti-TfR1 and anti-malondialdehyde (MDA) adduct antibodies were effective at reliably staining ferroptotic tumor cells in numerous cell culture and tissue contexts. In summary, these findings suggest that anti-TfR1 antibodies can be used to selectively label cells undergoing ferroptosis.
2020-03-10 | PXD017425 | Pride