SRSF10 promotes cisplatin resistance in bladder cancer via BIN1 Exon 12 retention and ANXA1 activation.

RNA alternative splicing is a fundamental post-transcriptional mechanism that plays a key role in generating protein diversity. Previous studies from our group have shown that overexpression SRSF10 could promote liver cancer cell proliferation and invasion. However, its involvement in bladder cancer remains poorly understood. In the present study, we investigated SRSF10 expression using data from TCGA and GEO databases, immunohistochemistry, and proteomics. Functional validation was performed through in vitro and in vivo experiments, RNA sequencing, and bioinformatics analysis. Additionally, Co-Immunoprecipitation was utilized to confirm the interaction between BIN1(12+) and ANXA1. Our results demonstrate that SRSF10 is overexpressed in bladder cancer, with its expression correlating with poor prognosis and advanced clinical stages. Functional assays revealed that SRSF10 knockdown significantly decreased cell proliferation and cisplatin IC50, while its overexpression had the opposite effect. These findings were further validated in xenograft models and clinical samples. Mechanistically, we show that SRSF10 induces the retention of BIN1 exon 12, resulting in the upregulation of the BIN1(12+) isoform. BIN1(12+) directly interacts with and activates ANXA1, thereby contributing to cisplatin resistance. In conclusion, SRSF10 enhances cisplatin resistance in bladder cancer through the BIN1(12+)/ANXA1 signaling axis, suggesting its potential as a therapeutic target for bladder cancer.