Knockdown of MCM8 inhibits development and progression of bladder cancer in vitro and in vivo

Cancer Cell International

Wei Zhu¹  Ke Jin²  Hongyi Zhou²  Fei Gao²  Zhuoqun Xu²  Jianfeng Shao² 

[1] Shengli Clinical Medical College of Fujian Medical University, 350001, Fuzhou, China;Department of Urology, Fujian Provincial Hospital, 350001, Fuzhou, China;Wuxi People’s Hospital Affiliated to Nanjing Medical University, 299 Qingyang Rd, 214023, Wuxi, China;

关键词: Bladder cancer;    MCM8;    Cell proliferation;    Cell apoptosis;    Cell migration;   

DOI  :  10.1186/s12935-021-01948-2

来源: Springer

【 摘 要 】

BackgroundBladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising. Minichromosome maintenance eight homologous recombination repair factor (MCM8), a newly discovered MCM family member, has been shown to be required for DNA replication. Unfortunately, little is known concerning the roles of MCM8 in bladder cancer.MethodsThe present study, we aimed at probing into the impacts and detailed mechanisms of MCM8 in bladder cancer progression. In this study, MCM8 expression level was detected through immunohistochemistry staining (IHC), qRT-PCR and Western blot assay. Silenced MCM8 cell models were constructed by lentivirus transfection. In vitro, the cell proliferation was evaluated by the MTT assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were determined by flow cytometry. Moreover, the Human Apoptosis Antibody Array assay was performed to analyze the alterations of apoptosis-related proteins. The in vivo experiments were conducted to verify the effects of MCM8 knockdown on the tumor growth of bladder cancer.ResultsThe results demonstrated that compared with normal adjacent tissues, MCM8 expression in bladder cancer tissues was strongly up-regulated. The up-regulation of MCM8 expression in bladder cancer may be a valuable independent prognostic indicator. Of note, MCM8 inhibition modulated the malignant phenotypes of bladder cancer cells. In terms of mechanism, it was validated that MCM8 knockdown made Akt, P-Akt, CCND1 and CDK6 levels down-regulated, as well as MAPK9 up-regulated.ConclusionsTaken together, our study demonstrated an important role of MCM8 in bladder cancer and created a rationale for the therapeutic potential of MCM8 inhibition in human bladder cancer therapy.

【 授权许可】

CC BY