RNA splicing dysregulation and the hallmarks of cancer

Dysregulated RNA splicing is a molecular feature that characterizes almost all tumor types. Cancer-associated splicing alterations arise from recurrent mutations and altered expression of trans-acting factors governing splicing catalysis and regulation. Cancer-associated splicing dysregulation can promote tumorigenesis via diverse mechanisms, contributing to increased cell proliferation, decreased apoptosis, enhanced migration and metastatic potential, resistance to chemotherapy and evasion of immune surveillance. Recent studies have identified specific cancer-associated isoforms that play critical roles in cancer cell transformation and growth and demonstrated the therapeutic benefits of correcting or otherwise antagonizing such cancer-associated mRNA isoforms. In addition, clinical-grade small molecules that modulate or inhibit RNA splicing have similarly been developed as promising anticancer therapeutics. Here, this review splicing alterations characteristic of cancer cell transcriptomes, dysregulated splicing’s contributions to tumor initiation and progression, and existing and emerging approaches for targeting splicing for cancer therapy.