Epigenetic Regulation by Androgen Receptor in Prostate Cancer

Abstract

Prostate cancer is the most commonly diagnosed cancer in men all over the world. Androgen receptor (AR) functions as a nuclear receptor to facilitate ligand-dependent transcriptional activation in the nucleus. Advanced prostate cancer is treated with androgen deprivation therapy (ADT) because androgen and AR signaling drive the prostate tumor growth and anti-apoptotic ability. Resistance to ADT in most tumors develops quickly, but AR continues to be active in relapsed tumors called castration-resistant prostate cancer (CRPC). Therefore, it is important to understand AR transcriptional mechanism and downstream signaling. Recent studies have shown the central role of chromatin structure and histone modifications in AR-mediated gene regulation. Furthermore, AR functions through interaction with several tissue-specific transcription factors such as forkhead box protein A1 (FOXA1). Interestingly, non-coding RNAs such as long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) modulate epigenetic status to promote AR function directly or indirectly and have central roles in prostate cancer progressions. The focus of this review is on the involvement of AR in epigenetic regulation in prostate cancer development and progression.