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学科主题: 临床医学
题名:
YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells
作者: Sheng, Xia1; Li, Wen-Bin1; Wang, De-Lin1; Chen, Ke-Hong1; Cao, Jian-Jia1; Luo, Zhao1; He, Jiang2; Li, Mei-Cai1; Liu, Wu-Jiang3; Yu, Chao4
关键词: Yes-associated protein ; TEA domain family member 1 ; prostate cancer ; PC-3 cell ; RNA interference
刊名: MOLECULAR MEDICINE REPORTS
发表日期: 2015-10-01
DOI: 10.3892/mmr.2015.4005
卷: 12, 期:4, 页:4867-4876
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Medicine, Research & Experimental
研究领域[WOS]: Oncology ; Research & Experimental Medicine
关键词[WOS]: TUMOR-SUPPRESSOR PATHWAY ; HIPPO PATHWAY ; SIZE-CONTROL ; CONTACT INHIBITION ; BANTAM MICRORNA ; GROWTH-CONTROL ; DROSOPHILA ; CARCINOMA ; PROMOTES ; FAMILY
英文摘要:

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.

语种: 英语
所属项目编号: 30972999
项目资助者: Natural Science Foundation of China
WOS记录号: WOS:000362999200009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58929
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400016, Peoples R China
2.Chongqing Med Univ, Univ Town Hosp, Dept Urol, Chongqing 401331, Peoples R China
3.Peking Univ, Hosp 1, Inst Urol, Dept Urol, Beijing 100034, Peoples R China
4.Chongqing Med Univ, Life Sci Res Inst, Dept Surg, Chongqing 400016, Peoples R China

Recommended Citation:
Sheng, Xia,Li, Wen-Bin,Wang, De-Lin,et al. YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells[J]. MOLECULAR MEDICINE REPORTS,2015,12(4):4867-4876.
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