The androgen receptor messenger RNA: what do we know?

The Androgen Receptor (AR), transcriptionally activated by its ligands, testosterone and dihydrotestosterone (DHT), is widely expressed in cells and tissues, influencing normal biology and disease states. The protein product of the AR gene is involved in the regulation of numerous biological functions, including the development and maintenance of the normal prostate gland and of the cardiovascular, musculoskeletal and immune systems. Androgen signalling, mediated by AR protein, plays a crucial role in the development of prostate cancer (PCa), and is presumed to be involved in other cancers including those of the breast, bladder, liver and kidney. Significant research and reviews have focused on AR protein function; however, inadequate research and literature exist to define the function of AR mRNA in normal and cancer cells. The AR mRNA transcript is nearly 11 Kb long and contains a long 3’ untranslated region (UTR), suggesting its biological role in post-transcriptional regulation, consequently affecting the overall functions of both normal and cancer cells. Research has demonstrated that many biological activities, including RNA stability, translation, cellular trafficking and localization, are associated with the 3’ UTRs of mRNAs. In this review, we describe the potential role of the AR 3’ UTR and summarize RNA-binding proteins (RBPs) that interact with the AR mRNA to regulate post-transcriptional metabolism. We highlight the importance of AR mRNA as a critical modulator of carcinogenesis and its important role in developing therapy-resistant prostate cancer.