Understanding aberrant RNA splicing to facilitate cancer diagnosis and therapy

Almost all genes in normal cells undergo alternative RNA splicing to generate a greater extent of diversification of gene products for normal cellular functions. RNA splicing is tightly regulated and closely interplays with genetic and epigenetic machinery. While DNA polymorphism and somatic mutations modulate alternative splicing patterns, RNA splicing also controls genomic stability, chromatin organization, and transcriptome. Tumor cells, in turn, often take advantage of aberrant RNA splicing to develop, grow and progress into therapy-resistant tumors. Understanding alternative RNA splicing in tumor cells would, therefore, provide us opportunities to gain further insights into tumor biology, identify diagnostic or prognosis biomarkers, as well as to design effective therapeutic means to control tumor progression. Here, we provide an overview of RNA splicing mechanisms and use prostate cancer as an example to review recent advancements in our understanding of RNA splicing in cancer progression and therapy resistance. We also discuss emerging diagnostic and therapeutic potentials of RNA splicing events or RNA splicing factors.