Wang Dailian, Chen Zhicong, Lin Fan, Wang Ziqiang, Gao Qunjun, Xie Haibiao, Xiao Huizhong, Zhou Yifan, Zhang Fuyou, Ma Yingfei, Mei Hongbin, Cai Zhiming, Liu Yuchen, Huang Weiren
Department of Urology, Shenzhen Second People's Hospital, Guangzhou Medical University, Guangdong, China.
Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen, China.
J Cancer. 2018 Nov 24;9(24):4684-4695. doi: 10.7150/jca.27381. eCollection 2018.
Opa interacting protein 5 (OIP5) has previously been identified as a tumorigenesis gene. The purpose of this study is to explore the role of OIP5 in the progression of bladder cancer (BC). The OIP5 expression and clinical behaviors in bladder cancer were collected from lager database. Our study showed that OIP5 was highly expressed in bladder cancer tissues and cells. Overexpression of OIP5 in tumor patients predicted worse overall survival (OS) and higher histological grade. Vitro and vivo experiments demonstrated that knockdown of OIP5 significantly inhibited cell growth of BC. Scratch assay and transwell assay suggested that migration capacity of BC cells was decreased after knockdown of OIP5. Cisplatin sensitivity assay indicated that depletion of OIP5 increased the sensitivity of BC cells to cisplatin. Finally, we identified 38 overlapping differentially expressed genes (DEGs) between RNA-seq and TCGA analyses which were closely linked to OIP5. Bioinformatics analysis showed that these DEGs enriched in oocyte meiosis, fanconi anemia pathway, cell cycle, and microRNAs regulation. TOP2A, SPAG5, SKA1, EXO1, TK1 were confirmed to associated with bladder cancer development. Our study suggests that OIP5 may be a potential biomarker for growth, metastasis and drug-resistance in bladder cancer.
OPA相互作用蛋白5（OIP5）先前已被鉴定为一种肿瘤发生基因。本研究的目的是探讨OIP5在膀胱癌（BC）进展中的作用。从大型数据库中收集了膀胱癌中OIP5的表达情况和临床行为。我们的研究表明，OIP5在膀胱癌组织和细胞中高表达。肿瘤患者中OIP5的过表达预示着总体生存期（OS）较差且组织学分级较高。体外和体内实验表明，敲低OIP5可显著抑制BC细胞的生长。划痕实验和Transwell实验表明，敲低OIP5后BC细胞的迁移能力降低。顺铂敏感性实验表明，OIP5的缺失增加了BC细胞对顺铂的敏感性。最后，我们在RNA测序和TCGA分析之间鉴定出38个重叠的差异表达基因（DEG），它们与OIP5密切相关。生物信息学分析表明，这些DEG富集于卵母细胞减数分裂、范可尼贫血通路、细胞周期和微小RNA调控。TOP2A、SPAG5、SKA1、EXO1、TK1被证实与膀胱癌的发生发展有关。我们的研究表明，OIP5可能是膀胱癌生长、转移和耐药性的潜在生物标志物。
