Dysregulation of mRNA splicing in urothelial carcinoma: Clinical, diagnostic and therapeutic implications

Alterations in mRNA splicing play a critical role in driving the molecular heterogeneity of many cancers, including urothelial carcinoma, by contributing to disease progression, treatment response, and clinical outcomes. These splicing changes can arise from somatic mutations in core spliceosomal components or through alternative splicing events affecting cancer-associated genes. In this review, we examine how dysregulation of pre-mRNA splicing influences key aspects of urothelial carcinoma biology, including cell proliferation, invasion, metastasis, modulation of the immune microenvironment, metabolism, and therapeutic resistance. We highlight frequently observed splicing-factor mutations and discuss the impact of aberrant splicing and cancer-specific isoforms on prognosis. We also explore splicing alterations associated with susceptibility to urothelial carcinoma and review emerging therapeutic strategies, such as splice-switching oligonucleotides and small molecule spliceosome inhibitors, that offer promising avenues for precision medicine in this disease.