Author Identifier (ORCID)
Aaron Beasley: https://orcid.org/0000-0001-5727-7463
Elin S. Gray: https://orcid.org/0000-0002-8613-3570
Abstract
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 Om-nibus (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 < 0.001). Its knockdown inhibited the proliferation, migration, and invasion abilities and promoted erastin-induced ferroptosis, as evidenced by increased reactive oxygen species (ROS), lipid peroxidation, and iron accumulation (all p < 0.05). 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.
Keywords
Bladder cancer, cisplatin resistance, ferroptosis, SLC3A2
Document Type
Journal Article
Date of Publication
1-28-2026
Volume
79
Issue
1
Publication Title
Archivos Espanoles De Urologia
Publisher
Iniestares, S.A.
School
Centre for Precision Health / School of Medical and Health Sciences
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
First Page
36
Last Page
48
Comments
Yang, Q., Zhou, D., Beasley, A., Liu, Y., Yan, Z., Fang, H., Li, Y., & Gray, E. S. (2026). Identification of SLC3A2 as a potential therapeutic target of ferroptosis in bladder cancer. Archivos Españoles De Urología, 79(1), 36–48. https://doi.org/10.56434/j.arch.esp.urol.20267901.5