RNA-binding motif protein 3 (RBM3) can be a potentially valuable predictive biomarker of chemotherapy response in muscle-invasive bladder cancer (MIBC), which could, if prospectively validated, enhance treatment stratification of patients with this aggressive disease.

• A cohort of 145 patients, 65 of whom were treated with NAC (neoadjuvant cisplatin-based chemotherapy), was used and in vitro analyses were conducted to determine the role of RBM3 in MIBC.

• In transurethral resection of the bladder vs cystectomy specimens, a significantly higher expression of RBM3 protein was detected; consistency in expression was found between primary tumors and lymph node metastases.

• A significantly decreased risk of recurrence and a prolonged cancer-specific survival and overall survival were noted in patients with high-tumor specific RBM3 expression vs NAC-untreated patients.

• Reduced sensitivity to cisplatin and gemcitabine in high-grade T24 human bladder carcinoma cells (which expressed higher RBM3 mRNA levels than RT4 cells) was induced by RBM3 silencing.

• In transcriptomic analysis, there was potential implication of RBM3 in facilitating cell cycle progression, in particular G ₁ /S-phase transition, and initiation of DNA replication.

• In siRBM3-transfected T24 cells, findings revealed a gathering of cells residing in the G ₁ -phase as well as altered levels of recognized regulators of G ₁ -phase progression, including Cyclin D1/CDK4 and CDK2.