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YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.
Mol Med Rep. 2015 Oct; 12(4):4867-76.MM

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+Show Affiliations

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, University‑Town Hospital of Chongqing Medical University, Chongqing 401331, P.R. China.Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.Department of Urology, Institute of Urology, First Hospital of Peking University, Beijing 100034, P.R. China.Department of Surgery, Life Science Research Institute of Chongqing Medical University, Chongqing 400016, P.R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26126522

Citation

Sheng, Xia, et al. "YAP Is Closely Correlated With Castration-resistant Prostate Cancer, and Downregulation of YAP Reduces Proliferation and Induces Apoptosis of PC-3 Cells." Molecular Medicine Reports, vol. 12, no. 4, 2015, pp. 4867-76.
Sheng X, Li WB, Wang DL, et al. YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells. Mol Med Rep. 2015;12(4):4867-76.
Sheng, X., Li, W. B., Wang, D. L., Chen, K. H., Cao, J. J., Luo, Z., He, J., Li, M. C., Liu, W. J., & Yu, C. (2015). YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells. Molecular Medicine Reports, 12(4), 4867-76. https://doi.org/10.3892/mmr.2015.4005
Sheng X, et al. YAP Is Closely Correlated With Castration-resistant Prostate Cancer, and Downregulation of YAP Reduces Proliferation and Induces Apoptosis of PC-3 Cells. Mol Med Rep. 2015;12(4):4867-76. PubMed PMID: 26126522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells. AU - Sheng,Xia, AU - Li,Wen-Bin, AU - Wang,De-Lin, AU - Chen,Ke-Hong, AU - Cao,Jian-Jia, AU - Luo,Zhao, AU - He,Jiang, AU - Li,Mei-Cai, AU - Liu,Wu-Jiang, AU - Yu,Chao, Y1 - 2015/06/29/ PY - 2014/08/19/received PY - 2015/05/19/accepted PY - 2015/7/2/entrez PY - 2015/7/2/pubmed PY - 2016/8/3/medline SP - 4867 EP - 76 JF - Molecular medicine reports JO - Mol Med Rep VL - 12 IS - 4 N2 - 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. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/26126522/YAP_is_closely_correlated_with_castration_resistant_prostate_cancer_and_downregulation_of_YAP_reduces_proliferation_and_induces_apoptosis_of_PC_3_cells_ L2 - http://www.spandidos-publications.com/mmr/12/4/4867 DB - PRIME DP - Unbound Medicine ER -