GOLPH3 is a potential therapeutic target and a prognostic indicator of poor survival in bladder cancer treated by cystectomy

2015 
// Qing Zhang 1, * , Junlong Zhuang 1, * , Yongming Deng 1, * , Xiaozhi Zhao 1 , Bo Tang 3 , Dongwei Yao 1 , Wei Zhao 4 , Cunjie Chang 4 , Qun Lu 1 , Wei Chen 1 , Shiwei Zhang 1 , Changwei Ji 1 , Lin Cao 2, 3 , Hongqian Guo 1 1 Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China 2 College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, PR China 3 Vazyme Biotech Co., Ltd, Nanjing 210000, Jiangsu, PR China 4 MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu 210061, China * These authors have contributed equally to this work Correspondence to: Hongqian Guo, e-mail: dr.guohongqian@gmail.com Keywords: bladder cancer, GOLPH3, AKT/mTOR signalling, prognosis, survival Received: March 16, 2015      Accepted: August 12, 2015      Published: August 22, 2015 ABSTRACT Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. However, its clinical significance and biological role in bladder cancer remains unclear. In this study, we sought to analyze the GOLPH3 expression in bladder cancer samples and cells, and explore its clinical significance and biological role. We found that GOLPH3 was significantly increased in bladder cancer tissues and cells. Overexpression of GOLPH3 had significant correlation with poorer survival for bladder cancer patients treated by cystectomy. Knockdown of GOLPH3 inhibited the proliferation, migration and invasion of cancer cells, and tumor growth in a xenograft mouse model. GOLPH3 silencing inhibited AKT/m-TOR signaling, increased the cyclin-dependent kinase (CDK) inhibitor p27 and decreased the CDK regulator cyclin D1 and matrix metallopeptidase 9 (MMP9). Thus, GOLPH3 is likely to play important roles in bladder cancer progression via modulating AKT/mTOR signaling, and it is a novel prognostic biomarker and promising therapeutic target for bladder cancer.
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