Alternative polyadenylation: An untapped source for prostate cancer biomarkers and therapeutic targets?

Abstract

Objective: To review alternative polyadenylation (APA) as a mechanism of gene regulation and consider potential roles for APA in prostate cancer (PCa) biology and treatment.

Methods: An extensive review of mRNA polyadenylation, APA, and PCa literature was performed. This review article introduces APA and its association with human disease, outlines the mechanisms and components of APA, reviews APA in cancer biology, and considers whether APA may contribute to PCa progression and/or produce novel biomarkers and therapeutic targets for PCa.

Results: Eukaryotic mRNA 3'-end cleavage and polyadenylation play a critical role in gene expression. Most human genes encode more than one polyadenylation signal, and produce more than one transcript isoform, through APA. Polyadenylation can occur throughout the gene body to generate transcripts with differing 3'-termini and coding sequence. Differences in 3'-untranslated regions length can modify post-transcriptional gene regulation by microRNAs and RNA binding proteins, and alter mRNA stability, translation efficiency, and subcellular localization. Distinctive APA patterns are associated with human diseases, tissue origins, and changes in cellular proliferation rate and differentiation state. APA events may therefore generate unique mRNA biomarkers or therapeutic targets in certain cancer types or phenotypic states.

Conclusions: The full extent of cancer-associated and tissue-specific APA events have yet to be defined, and the mechanisms and functional consequences of APA in cancer remain incompletely understood. There is evidence that APA is active in PCa, and that it may be an untapped resource for PCa biomarkers or therapeutic targets.

Keywords: 3′-untranslated region; Alternative polyadenylation; Intronic polyadenylation; Polyadenylation; Prostate cancer; microRNA.