SLC9A3R1 Promotes Bladder Cancer Progression Through Regulation of Malignant Phenotypes: Integrated Bioinformatics Analysis and Experimental Validation

BACKGROUND: SLC9A3R1 is a PDZ domain-containing scaffolding protein, but its role in bladder cancer remains unclear. METHODS: This study analyzed publicly available pan-cancer datasets to characterize the expression patterns and prognostic significance of SLC9A3R1, and further explored its associated biological processes, pathways, and immune cell infiltration via differential expression, enrichment, and CIBERSORT analyses. Functional knockdown experiments in bladder cancer cell lines were also performed to assess the impact of SLC9A3R1 silencing on mTOR signaling and cellular activities. RESULTS: SLC9A3R1 was abnormally expressed across multiple tumor types, and its prognostic value differed among tumors. High SLC9A3R1 expression was linked to worse clinical outcomes in several distinct bladder cancer cohorts. SLC9A3R1-associated gene profiles were linked to immunological control, metabolic activities, cell cycle regulation, DNA replication and repair, and epithelial differentiation, according to functional enrichment analysis. CIBERSORT analysis further revealed associations between SLC9A3R1 expression and the infiltration levels of multiple immune cell populations in bladder cancer. SLC9A3R1 knockdown was shown to inhibit bladder cancer cell migration and proliferation in vitro, along with decreased levels of p-mTOR and p-S6. CONCLUSIONS: SLC9A3R1 may promote bladder cancer progression through mTOR signaling and represents a potential prognostic biomarker and therapeutic target.