通过通过MAD2L2调节p53DNA损伤反应途径,AURKB促进了膀癌的进展
Linzhi Li1, Pengcheng Jiang1, Weimin Hu1
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Journal of translational medicine
|March 22, 2024
概括
极光激酶B (AURKB) 和MAD2L2通过降低p53 DNA损伤反应途径来促进膀癌 (BC) 的进展. 准AURKB可能为膀癌提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 膀癌 (BC) 是尿路的一种常见恶性瘤.
- 极光激酶B (AURKB) 和MAD2L2在癌症中过度表达,并促进瘤生长.
- 对于AURKB和MAD2L2在BC进展中的特定作用以及它们的相互作用机制尚不清楚.
研究的目的:
- 为了研究AURKB和MAD2L2在膀癌中的相互作用.
- 阐明AURKB和MAD2L2通过DNA损伤反应 (DDR) 途径影响BC进展的潜在机制.
主要方法:
- 对BC患者数据的生物信息分析.
- 在体外测试 (CCK-8,殖民地形成,流细胞计,衰老染色,迁移,入侵).
- 在体内异种移植小鼠模型,西部斑,共免疫沉和RT-qPCR.
主要成果:
- AURKB在BC中表达很高,与预后差以及MAD2L2表达相关.
- AURKB与MAD2L2相互作用并调节MAD2L2的表达,促进BC细胞的增殖,迁移,入侵和细胞周期的进展.
- 在AURKB中,AURKB knockdown诱导衰老,这种效应被MAD2L2过度表达所逆转;MAD2L2中,MAD2L2的 knockdown模仿了AURKB的 knockdown效应.
- 缺乏p53可挽救MAD2L2 knockdown诱导的增殖抑制,细胞循环停止和衰老.
结论:
- AURKB激活MAD2L2表达,导致p53 DDR通路下调,并促进BC进展.
- AURKB代表了潜在的分子标记物和膀癌的治疗标.
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