Zhou Junhao, Tian Hu, Zhi Xi, Xiao Zhuoyu, Chen Taoyi, Yuan Haoyu, Chen Qi, Chen Mingkun, Yang Jiankun, Zhou Qizhao, Xue Kangyi, Guo Wenbin, Xia Ming, Bao Jiming, Yang Cheng, Duan Haifeng, Wang Hongyi, Huang Zhipeng, Zhu Ting, Liu Cundong
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, Guangdong, People's Republic of China.
Department of Urology, The First People's Hospital of Zhaoqing, Zhaoqing, 526020, China.
Cancer Cell Int. 2021 Dec 11;21(1):660. doi: 10.1186/s12935-021-02315-x.
In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear.
Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses.
ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway.
This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.
在膀胱癌中，高达70%的患者在切除术后5年内会复发，其中复发的潜在机制在很大程度上仍不清楚。
进行了定量实时聚合酶链反应、蛋白质免疫印迹和免疫组织化学检测。进一步进行肿瘤球形成和肿瘤异种移植试验，以评估激活转录因子5（ATF5）的潜在生物学作用。进行染色质免疫沉淀-聚合酶链反应和荧光素酶活性测定，以探索潜在的分子机制。采用双尾配对t检验、χ检验、Kaplan Meier和Cox回归分析以及Spearman等级相关系数进行统计分析。
ATF5在膀胱尿路上皮癌（BLCA）组织中升高，尤其是在复发性BLCA中，这预示着预后不良。过表达ATF5显著增强了膀胱癌细胞的肿瘤球形成能力，而沉默ATF5则抑制了该能力。从机制上讲，ATF5可以直接结合并刺激DVL1基因的启动子，从而激活Wnt/β-连环蛋白通路。
本研究为BLCA高复发潜能的部分机制提供了新的见解，表明ATF5可作为BLCA复发的预后因素或潜在治疗靶点。
