摘要
Recent evidence links BK polyomavirus (BKPyV) infection to an increased risk of bladder cancer. This study investigates the role of BKPyV and its microRNA, miR-B1, in cisplatin-induced apoptosis. PCR analysis detected BKPyV DNA in 3 of 22 urothelial carcinoma (UC) samples from a non-transplant population. Bladder cancer cells infected with BKPyV showed increased proliferation and miR-B1–3p and −5p expression. Bioinformatics analysis identified a miR-B1–5p target site in the 3′-UTR of activating transcription factor 3 (ATF3), confirmed by a luciferase assay. The inhibitory effect was further validated by reduced ATF3 mRNA levels following overexpression of miR-B1 vectors or 5p mimics. Cisplatin treatment upregulated ATF3 expression, as shown by qPCR and immunoblotting. Overexpression of ATF3 mitigated the cisplatin-induced reduction in cell viability and elevated apoptotic markers, including cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). BKPyV infection or large T antigen (TAg) overexpression suppressed cisplatin-induced ATF3 expression, reducing its cytotoxicity and apoptotic marker expression. However, overexpression of ATF3 in BKPyV-infected bladder cancer cells attenuated BKPyV's inhibitory effects, restoring cisplatin-induced cytotoxicity and apoptotic marker expression, suggesting BKPyV infection promotes resistance to cisplatin cytotoxicity. Transfection with miR-B1 vectors or miR-B1–5p mimics decreased cisplatin-induced annexin V-positive cells, caspase-3 activity, and apoptotic marker expression, indicating that miR-B1 suppresses cisplatin-induced apoptosis. In conclusion, this study demonstrates that BKPyV promotes bladder cancer cell growth and impairs cisplatin-induced apoptosis, with miR-B1 targeting ATF3 as a key mechanism. Targeting BKPyV replication or regulating miR-B1 expression could offer potential therapeutic strategies for managing BKPyV-positive and cisplatin-resistant urothelial carcinoma. © 2025