HSPE1 Inhibits Bladder Cancer Ferroptosis via a Glutathione-Dependent Mechanism by Suppressing GPX4

Bladder cancer (BLCA) remains a significant health risk despite advancements in medical science that have led to reduced incidence and death rates. While the molecular regulatory mechanisms of BLCA are not yet fully understood, HSPE1, a member of the heat shock protein family, is regarded as a reliable prognostic target for BLCA. Using data from The Cancer Genome Atlas (TCGA) database, the differential expression levels of HSPE1 and its relationship to GPX4 were examined. Gene Set Enrichment Analysis was used to carry out HSPE1 pathway enrichment analysis. HSPE1 and GPX4 expressions in cells were assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. Cell cycle alternations and apoptosis were evaluated using flow cytometry. Cell proliferation was assessed using EdU and colony formation assays. The lactate dehydrogenase (LDH) test, glutathione (GSH) measurement, and Liperfluo assay were utilized to evaluate the presence of ferroptosis in cells. BLCA tissues and cells had significantly elevated levels of HSPE1. In BLCA, high expression of HSPE1 inhibited apoptosis while promoting cell proliferation and cell cycle progression. Significant enrichment of HSPE1 was found in the GSH metabolism and ferroptosis pathways, according to pathway enrichment analysis. In cancer cells, HSPE1 promoted GSH accumulation, decreased lipid peroxidation, and inhibited cell ferroptosis, as demonstrated in a rescue experiment with the ferroptosis inhibitor Fer-1. Pearson correlation analysis unveiled a substantial positive correlation between HSPE1 and the ferroptosis regulator GPX4. According to the results of rescue experiments, HSPE1 regulated GPX4 to affect cell lipid peroxidation levels and GSH accumulation. HSPE1 plays a crucial role in regulating GPX4 to prevent BLCA cells from undergoing ferroptosis, with this control mechanism dependent on GSH

Apoptosis · Biology · Cancer · Cancer cell · Cell cycle · Cell growth · Enzyme · Glutathione · Glutathione peroxidase · GPX4 · Lipid peroxidation · Oxidative stress · Programmed cell death · Cancer, Lipids, and Metabolism · Ferroptosis and cancer prognosis · RNA modifications and cancer · Biochemistry · Cancer Research · Genetics · Molecular Biology

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