The evolution of long noncoding RNA acceptance in prostate cancer initiation, progression, and its clinical utility in disease management

Abstract

CONTEXT: It is increasingly evident that non-protein-coding regions of the genome can give rise to transcripts that form functional layers of the cancer genome. One of most abundant classes in these regions is long noncoding RNAs (lncRNAs). They have gained increasing attention in prostate cancer (PCa) and paved the way for a greater understanding of these cryptic regulators in cancer. OBJECTIVE: To review current research exploring the functional biology of lncRNAs in PCa over the past three decades. EVIDENCE ACQUISITION: A systematic review was performed using PubMed to search for reports with terms "long noncoding RNA", "prostate", and "cancer" over the past 30 yr (1988-2018). EVIDENCE SYNTHESIS: We comprehensively surveyed the literature collected and summarise experiments leading to the characterisation of lncRNAs in PCa. A historical timeline of lncRNA identification is described, where each lncRNA is categorised mechanistically and within the primary areas of carcinogenesis: tumour risk and initiation, tumour promotion, tumour suppression, and tumour treatment resistance. We describe select lncRNAs that exemplify these areas. We also review whether these lncRNAs have a clinical utility in PCa diagnosis, prognosis, and prediction, and as therapeutic targets. CONCLUSIONS: The biology of lncRNA is multifaceted, demonstrating a complex array of molecular and cellular functions. These studies reveal that lncRNAs are involved in every stage of PCa. Their clinical utility for diagnosis, prognosis, and prediction of PCa is well supported, but further evaluation for their therapeutic candidacy is needed. We provide a detailed resource and view inside the lncRNA landscape for other cancer biologists, oncologists, and clinicians. PATIENT SUMMARY: In this study, we review current knowledge of the non-protein-coding genome in prostate cancer (PCa). We conclude that many of these regions are functional and a source of accurate biomarkers in PCa. With a strong research foundation, they hold promise as future therapeutic targets, yet clinical trials are necessary to determine their intrinsic value to PCa disease management.