YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells

Abstract

Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life-threatening androgen-resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC-3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC-3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para-PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour-node-metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell-cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated.

Silencing circular RNA circZNF609 restrains growth, migration and invasion by up-regulating microRNA-186-5p in prostate cancer

“…The YAP1 and AMPK signaling pathways play momentous parts in tumour [25,26]. Previous studies had reported that YAP1 and AMPK pathways are activated in PC and the two pathways are involved in the pathogenesis of PC [27,28]. Research demonstrated circ0023404 exerted its efficacy via YAP1 signaling pathways [29] and other research demonstrated that circ0008274 exerted its efficacy by AMPK signaling pathway [30].…”

High expression of citron kinase predicts poor prognosis of prostate cancer

“…RT-qPCR. The isolation of total RNA and RT-qPCR were performed as described previously (19). All samples were amplified in triplicate.…”

YAP knockdown inhibits proliferation and induces apoptosis of human prostate cancer DU145 cells

“…Increasing evidence has suggested the important roles of YAP in regulating PCa cell behavior (18,19). To the best our knowledge, no previous study has focused on the role of YAP within human PCa DU145 cells.…”