Androgen Receptor Blockade Using Enzalutamide Suppresses Long Non-Coding RNA ARLNC1 in Prostate Cancer Cells

Abstract

Prostate cancer (PCa) is a common malignant disease with high mortality rates that develops and progresses in anandrogen-dependent way. In recent years, RNA sequencing enabled identification of many PCa-related long noncodingRNAs including androgen receptor-regulated long non-coding RNA 1 (ARLNC1) and prostate cancer-associatedtranscript 1 (PCAT1). In the present study, our goal was to illuminate expression changes of ARLNC1 and PCAT1 inthe context of androgen stimulation or androgen receptor (AR) blockade with respect to AR expression status. In thisexperimental study, LNCaP cells and higher AR-expressing LNCaP-AR++ cells were used as cell models. Cells weretreated with dihydrotestosterone (DHT) as an androgen stimulator and/or enzalutamide as an AR inhibitor. Cell viabilitywas assessed using annexin V and propidium iodide (PI) staining in flow cytometry. Androgen stimulation promptedbaseline ARLNC1 levels by 53.5-fold in the LNCaP cells (P=0.01) and by 25-fold in the LNCAP-AR+ cells (P=0.18). ARinhibition by enzalutamide reduced baseline ARLNC1 in LNCaP-AR++ cells by 2-fold (P=0.01), but to a lesser extentin LNCaP cells. Co-treatment of cells with DHT and enzalutamide led to a remarkable decrease in the DHT effect onARLNC1 expression. No specific effect of androgen stimulation or AR blockade on PCAT1 expression was detected.Our results revealed that the extent of induction of ARLNC1 by androgen is modulated by receptor expression status.In addition, we determined that AR blockade, via enzalutamide, effectively suppresses ARLNC1 both at baseline andafter induction by DHT.

Keywords

• androgen
• androgen receptor
• enzalutamide
• long non-coding rnas
• prostate cancer