Zhang Qing, Zhuang Junlong, Deng Yongming, Zhao Xiaozhi, Tang Bo, Yao Dongwei, Zhao Wei, Chang Cunjie, Lu Qun, Chen Wei, Zhang Shiwei, Ji Changwei, Cao Lin, Guo Hongqian
Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
Vazyme Biotech Co., Ltd, Nanjing 210000, Jiangsu, PR China.
Oncotarget. 2015 Oct 13;6(31):32177-92. doi: 10.18632/oncotarget.4867.
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.
高尔基体磷蛋白3（GOLPH3）已被报道参与多种人类癌症的发展。然而，其在膀胱癌中的临床意义和生物学作用仍不清楚。在本研究中，我们试图分析GOLPH3在膀胱癌样本和细胞中的表达，并探讨其临床意义和生物学作用。我们发现GOLPH3在膀胱癌组织和细胞中显著增加。GOLPH3的过表达与接受膀胱切除术治疗的膀胱癌患者较差的生存率显著相关。敲低GOLPH3可抑制癌细胞的增殖、迁移和侵袭，以及异种移植小鼠模型中的肿瘤生长。GOLPH3沉默抑制了AKT/m-TOR信号传导，增加了细胞周期蛋白依赖性激酶（CDK）抑制剂p27，并降低了CDK调节因子细胞周期蛋白D1和基质金属肽酶9（MMP9）。因此，GOLPH3可能通过调节AKT/mTOR信号传导在膀胱癌进展中发挥重要作用，并且它是一种新型的预后生物标志物和有前景的膀胱癌治疗靶点。
