title: 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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: De-Lin
authors.initials: DL
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ke-Hong
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jian-Jia
authors.initials: JJ
authors.lastname: Cao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Urology, University‑Town Hospital of Chongqing Medical University, Chongqing 401331, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Mei-Cai
authors.initials: MC
authors.lastname: Li
authors.affiliation: Department of Urology, Institute of Urology, First Hospital of Peking University, Beijing 100034, P.R. China.
authors.forename: Wu-Jiang
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: Department of Surgery, Life Science Research Institute of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human