Background: Bladder cancer (BC) represents the most prevalent malignancy within the urinary system. Mounting evidence underscores the critical involvement of ferroptosis in cancer pathogenesis; Consequently, this study delves into its molecular underpinnings and therapeutic potential specifically in BC. Methods: We analyzed gene expression profiles from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) repositories. Ferroptosis-related genes (FRGs) were selected from the FerrDb database. Utilizing systematic bioinformatics analyses, we identify differentially expressed and prognostic FRGs and construct an FRGs prognostic model. Combined with protein-protein interaction (PPI) analysis, solute carrier family 3 member 2 (SLC3A2) was selected for further study. Following targeted small interfering RNA (siRNA)-mediated knockdown of SLC3A2 in BC cell lines, we conducted comprehensive functional assays to evaluate its effect on malignant phenotypes, ferroptosis, and cisplatin sensitivity. Results: SLC3A2 expression was significantly elevated in BC cells (p p SLC3A2 depletion also enhanced cisplatin sensitivity. Conclusions: Collectively, these findings establish SLC3A2 as playing a vital oncogenic role in BC tumorigenesis and progression. Its function in inhibiting ferroptosis—especially during cisplatin-based chemotherapy—makes it a promising therapeutic target.
Yang et al. (Thu,) studied this question.