RNA Splicing Dysregulation and Nonsense-Mediated mRNA Decay in Urological Cancers: From Molecular Mechanisms to Biomarkers and Therapeutic Targets

Urological cancers include prostate, bladder, and kidney cancers, as well as testicular, ureteral, urethral, and penile tumors. Large-scale sequencing has mapped many of their genetic and epigenetic changes. Attention is now turning to post-transcriptional regulation, especially alternative pre-mRNA splicing and nonsense-mediated mRNA decay (NMD). Splicing can generate transcripts with premature termination codons, and NMD determines whether those transcripts persist, shaping the protein isoforms that tumor cells express.Growing evidence links altered splicing factors, spliceosome activity, and isoform switching to tumor aggressiveness, immune evasion, and treatment resistance. These processes may yield clinically useful biomarkers and therapeutic targets. In prostate cancer, the androgen receptor variant AR-V7 is associated with resistance to abiraterone and enzalutamide in metastatic castration-resistant disease and has been prospectively evaluated as a circulating tumor cell biomarker. In bladder cancer, PTBP1 promotes progression through altered splicing of MEIS2 and PKM. In clear cell renal cell carcinoma, coordinated intron retention and poison-exon inclusion illustrate how splicing and NMD interact. This Research Topic will bring these findings together across urological cancers and connect molecular mechanisms with outcomes such as early detection, risk stratification, and treatment response.We welcome hypothesis-driven laboratory studies, rigorous bioinformatic analyses, and translational research, including well-designed studies with negative or contradictory findings. We also welcome articles on work in progress that state the hypothesis, proposed approach, unresolved questions, and limitations. Mechanistic studies need not include patient-outcome data if they directly address the Research Topic. Sharing of code, pipelines, and datasets is encouraged.Topics of interest include, but are not limited to:- Mutations, expression, or activity changes in splicing factors, spliceosome components, and NMD regulators (including RNA-binding proteins, exon-junction complex components, and UPF/SMG factors) across urological cancers.- Functional studies of oncogenic isoform switches such as AR-V7, intron retention, cryptic splice-site usage, and poison-exon inclusion, including changes with tumor heterogeneity, microenvironment, and treatment over time.- NMD control of isoform abundance, tumor immunogenicity, and neoantigen presentation.- Splice-switching oligonucleotides, spliceosome inhibitors, and NMD-modulating strategies, including resistance, tumor selectivity, delivery, and effects on normal tissue.- Splicing- or NMD-based biomarkers in blood, urine, or tissue, including analytical performance, prognostic versus predictive value, independent validation, and added value beyond established clinical measures.- Computational and sequencing methods (bulk, single-cell, or long-read) for isoform quantification and splicing-event detection, including approaches that separate changes in splice-site usage from changes in transcript stability or cellular composition.- Alternative cleavage and polyadenylation, RNA editing, m6A and other RNA modifications, and circular or non-coding RNAs, where they clearly connect to splicing or NMD. Topic editors: Gopalakrishnan Chandrasekaran, Nidhi Shukla, Baotong Zhang Source: https://www.frontiersin.org/research-topics/86454/rna-splicing-dysregulation-and-nonsense-mediated-mrna-decay-in-urological-cancers-from-molecular-mechanisms-to-biomarkers-and-therapeutic-targets