The role of splicing factor SRSF3 in cancer progression: Mechanisms, biomarkers, and therapeutic implications

Alternative splicing is increasingly recognized as a critical layer of oncogenic regulation, yet the biological meaning of individual splicing factors remains highly context dependent. Serine/arginine-rich splicing factor 3 (SRSF3) has been widely described as an oncogenic splicing regulator in colorectal, cervical, lung, pancreatic, and other cancers; however, emerging evidence also suggests tumor-suppressive or context-specific functions in selected malignancies. This review critically evaluates current knowledge of SRSF3 in cancer by moving beyond a catalogue of downstream targets. We discuss how SRSF3 controls cancer-associated splicing programs, how these events intersect with signaling pathways, metabolism, immune regulation, and therapeutic resistance, and why the same factor may produce divergent biological outcomes depending on tumor lineage, RNA-binding partners, and target isoforms. We also examine unresolved controversies, including whether SRSF3 is a universal oncogenic driver or a context-dependent regulator, whether SRSF3 expression alone is sufficient as a biomarker, and how cancer-specific splicing events can be therapeutically targeted without disrupting essential RNA processing in normal tissues. Finally, we highlight translational barriers, including limited clinical validation, delivery challenges for RNA-based therapeutics, toxicity risks, and compensatory splicing networks. A more precise understanding of SRSF3-dependent splicing vulnerabilities may support future biomarker development and rational combination therapies.