AURKB promotes bladder cancer progression by deregulating the p53 DNA damage response pathway via MAD2L2

作者：Linzhi Li, Pengcheng Jiang, Weimin Hu, Fan Zou, Ming Li, Ting Rao, Yuan Ruan, Weimin Yu, Jinzhuo Ning, Cheng Fan · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05099-6 · 被引用次数：27 · 研究领域：Microtubule and mitosis dynamics、Protein Degradation and Inhibitors、Cancer Genomics and Diagnostics

BACKGROUND: Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer. However, the relationship between these factors and the mechanisms underlying their oncogenic activity in BC remains largely unknown. The present study aimed to explore the interactions between AURKB and MAD2L2 and how they affect BC progression via the DNA damage response (DDR) pathway. METHODS: Bioinformatics was used to analyze the expression, prognostic value, and pro-tumoral function of AURKB in patients with BC. CCK-8 assay, colony-forming assay, flow cytometry, SA-β-gal staining, wound healing assay, and transwell chamber experiments were performed to test the viability, cell cycle progression, senescence, and migration and invasion abilities of BC cells in vitro. A nude mouse xenograft assay was performed to test the tumorigenesis ability of BC cells in vivo. The expression and interaction of proteins and the occurrence of the senescence-associated secretory phenotype were detected using western blot analysis, co-immunoprecipitation assay, and RT-qPCR. RESULTS: AUR...