title: YAP is overexpressed in clear cell renal cell carcinoma and its knockdown reduces cell proliferation and induces cell cycle arrest and apoptosis.
abstract: Yes-associated protein (YAP) has been reported to be an oncogene in a number of malignancies. It constitutes an important regulatory mechanism for the Hippo pathway, a key regulator of cell growth and apoptosis. The present study aimed to investigate the clinical significance and the role of YAP in the development of clear cell renal cell carcinoma (ccRCC). YAP expression levels were compared between ccRCC and adjacent normal renal tissues by RT-PCR and immunohistochemistry, respectively. YAP expression levels were then detected in ccRCC cell lines 786-0 and ACHN, as well as in human embryonic kidney 293 cells (HEK-293) using western blotting. Three specific YAP-shRNA lentiviral vectors were constructed and transfected into 786-0 cells, and then the mRNA and protein levels of YAP and downstream transcription factor TEAD1 were detected. Finally, the effects of YAP silencing on proliferation and the cell cycle distribution of 786-0 cells were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM), respectively. The apoptosis rate was also analyzed by FCM. It was observed that the expression levels of YAP mRNA and protein in ccRCC tissues were higher than these levels in the adjacent normal renal tissues. The expression of YAP protein in ccRCC tissues was significantly correlated with clinical stage and differentiation. The YAP protein levels in the two ccRCC cell lines 786-0 and ACHN were significantly higher than that in the HEK-293 cells. Additionally, treatment of 786-0 cells with YAP-shRNA lentiviral vectors significantly reduced the expression levels of YAP and TEAD1 mRNA and protein. Further analyses in 786-0 cells in which YAP was decreased, revealed that cell proliferation was inhibited, cell cycle was arrested at the G1 phase and apoptosis was increased. These results indicate that YAP is an underlying oncogene in ccRCC and it may be a promising biomarker and therapeutic target of ccRCC.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 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, P.R. China.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Zhao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 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, 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, 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, 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, P.R. China.
authors.forename: Mei-Cai
authors.initials: MC
authors.lastname: Li
authors.affiliation: Institute of Urology, First Hospital of Peking University, Beijing, P.R. China.
authors.forename: Wu-Jiang
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: Gastroenterology and Neurology Center, University-Town Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins; D012333:RNA, Messenger / Q000235:genetics*; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human