Department of Urology, Beijing Friendship Hospital, No. 95 Yong'an Road, Xicheng District, Beijing, 100050, PR China.
Biomed Pharmacother. 2020 Jun;126:110066. doi: 10.1016/j.biopha.2020.110066. Epub 2020 Mar 12.
As one of the most common genitourinary malignancies worldwide, bladder cancer affects about 3.4 million people globally, with 430,000 new cases a year since 2015. Despite the advances in bladder cancer diagnosis and therapy, there has been little progress in the patients' overall survival in nearly 30 years. Therefore, investigating novel molecular therapeutic targets is required to gain insight into the tumorigenesis of bladder cancer, which ultimately may be used to develop more effective therapeutic strategies.
Herein, we used gene knockdown in vitro and in vivo to unveil the unknown roles of ZSCAN16 in bladder cancer. Afterward, to decipher the unknown regulatory role of ZSCAN16 in tumor progression, we verified that a bunch of genes including NF-κB, AKT, mTOR, and P38 were the key downstream regulators of ZSCAN16 by western blot and rescue experiments.
We found high expression of ZSCAN16 transcripts in bladder cancer cells and tumor samples from the TCGA database and tissue microarray bank, demonstrated in correlation with poor prognosis for bladder cancer patients. The in vitro experiments indicated that the silencing of ZSCAN16 by shRNA lentivirus promoted apoptosis and inhibited proliferation, colony formation, as well as migration and invasion in T24 cells. By investigating the signaling pathways, we proved ZSCAN16 play a novel role as oncogenic gene in bladder cancer by regulating NF-κB, AKT, mTOR, P38 and other genes. Furthermore, the in vivo experiments identified that ZSCAN16 knockdown retarded the tumor growth in nude mice.
In summary, these findings revealed that ZSCAN16 is a potential novel oncogene in the development and progression of bladder cancer. This study will shed light on developing novel therapeutic targets in the future treatment of bladder cancer.
膀胱癌是全球最常见的泌尿系统恶性肿瘤之一，全球约有 340 万人患病，自 2015 年以来，每年新增病例约 43 万例。尽管在膀胱癌的诊断和治疗方面取得了进展，但近 30 年来患者的总体生存率几乎没有提高。因此，需要研究新的分子治疗靶点，以深入了解膀胱癌的发生机制，最终可能用于开发更有效的治疗策略。
本文通过体外和体内基因敲低的方法揭示了 ZSCAN16 在膀胱癌中的未知作用。随后，为了解释 ZSCAN16 在肿瘤进展中的未知调控作用，我们通过 Western blot 和挽救实验验证了 NF-κB、AKT、mTOR 和 P38 等一系列基因是 ZSCAN16 的关键下游调控因子。
我们从 TCGA 数据库和组织微阵列库中发现膀胱癌细胞和肿瘤样本中 ZSCAN16 转录本高表达，与膀胱癌患者的预后不良相关。体外实验表明，shRNA 慢病毒沉默 ZSCAN16 可促进 T24 细胞凋亡，抑制增殖、集落形成以及迁移和侵袭。通过研究信号通路，我们证明 ZSCAN16 通过调节 NF-κB、AKT、mTOR、P38 等基因在膀胱癌中发挥致癌基因的新作用。此外，体内实验表明 ZSCAN16 敲低可抑制裸鼠肿瘤生长。
综上所述，这些发现表明 ZSCAN16 是膀胱癌发生和进展的潜在新致癌基因。本研究将为未来膀胱癌的治疗提供新的治疗靶点。
