Alternative polyadenylation in cancer: Molecular mechanisms and clinical application

Abstract

Alternative polyadenylation (APA) serves as a crucial mechanism for the posttranscriptional regulation of gene expression and influences gene expression by generating diverse mRNA isoforms. This process is regulated by a diverse array of RNA-binding proteins (RBPs), which selectively bind to specific sequences or structures within the pre-mRNA molecule. Dysregulation of APA and its associated RBPs has been implicated in numerous diseases, including cardiovascular diseases, nervous system disease, and cancer. For instance, aberrant APA events have been observed in several types of tumors, contributing to tumor heterogeneity and affecting key cellular pathways involved in cell proliferation, invasion, metastasis, and response to therapy. This review critically evaluates the current understanding of APA mechanisms and the multifaceted roles of RBPs in orchestrating this intricate process. We highlight recent advancements in high-throughput sequencing and bioinformatics tools that have enhanced our ability to study APA on a genome-wide scale. Moreover, we explored the pathological consequences of APA dysregulation, emphasizing its role in oncogenesis. By elucidating the intricate relationships between APA and RBPs, this review aims to underscore the potential of targeting the APA machinery and RBPs for therapeutic intervention. Understanding these molecular processes holds promise for developing novel diagnostic markers and treatment strategies for a range of human cancers.