title: GOLPH3 is a potential therapeutic target and a prognostic indicator of poor survival in bladder cancer treated by cystectomy.
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.
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Junlong
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Vazyme Biotech Co., Ltd, Nanjing 210000, Jiangsu, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Yao
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Cunjie
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Ji
authors.affiliation: College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, PR China.|Vazyme Biotech Co., Ltd, Nanjing 210000, Jiangsu, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Guo
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015653:Cystectomy / Q000009:adverse effects / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012189:Retrospective Studies; D012307:Risk Factors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery*
chemical_list: D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: AKT/mTOR signalling; GOLPH3; bladder cancer; prognosis; survival