Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death among men in the United States. Androgen receptor (AR) signaling is the dominant oncogenic pathway in PCa and the main strategy of PCa treatment is to control the AR activity. A large number of patients acquire resistance to Androgen deprivation therapy (ADT) due to AR aberrant activation, resulting in castration-resistant prostate cancer (CRPC). Understanding the molecular mechanisms underlying AR signaling in the PCa is critical to identify new therapeutic targets for PCa patients. The recent advances in high-throughput RNA sequencing (RNA-seq) techniques identified an increasing number of non-coding RNAs (ncRNAs) that play critical roles through various mechanisms in different diseases. Some ncRNAs have shown great potentials as biomarkers and therapeutic targets. Many ncRNAs have been investigated to regulate PCa through direct association with AR. In this review, we aim to comprehensively summarize recent findings of the functional roles and molecular mechanisms of AR-related ncRNAs as AR regulators or targets in the progression of PCa.
Highlights
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second-highest cause of cancer death among men in the United States, with an estimated 248,530 new cases and 34,130 deaths expected in 2021 in the United States (Siegel et al, 2021)
LncRNAs and circRNAs might mutually affect the binding with the same targets, which may be due to the RNA sequence similarity between long ncRNAs (lncRNAs) and circRNAs, or RNA structure-induced protein conformational change
A growing number of novel discovered non-coding RNAs (ncRNAs) and various research has revealed the crucial roles of ncRNAs in different disease processes
Summary
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second-highest cause of cancer death among men in the United States, with an estimated 248,530 new cases and 34,130 deaths expected in 2021 in the United States (Siegel et al, 2021). AR and its downstream signal cascades are critical for the initiation and progression of both localized and advanced metastatic PCa (Scher and Sawyers, 2005). The testing of prostate-specific antigen (PSA), a prototypic AR target, has been used for years as a diagnostic biomarker for the disease (Lilja et al, 2008). Androgen deprivation therapy (ADT) by AR antagonists and chemical castration is the standard treatment for patients with biochemical recurrence after primary therapy or with locally advanced or metastatic disease (Feldman and Feldman, 2001). Patients with metastasis-free PCa have a 100% 5-year survival rate (Brawley, 2012). The majority of primary cancers will eventually acquire ADT resistance and progress to castration-resistant prostate cancer (CRPC) (Kirby et al, 2011).
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