FOXM1/DEPDC1反循环促进肝癌发生,是癌症治疗的有希望的标
Teng Wei1, Chenquan Zeng1, Qineng Li1
1Cytotherapy Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
Cancer science
|July 15, 2024
概括
叉头盒 M1 (FOXM1) 和含有 1 (DEPDC1) 轴的 DEP 域驱动癌症生长和肝细胞癌的不良结果. 用T细胞受体工程的T细胞准这个轴对免疫治疗有希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫治疗是一种免疫疗法.
背景情况:
- 叉头盒M1 (FOXM1) 是线粒分裂的关键调节者,也是涉及各种人类癌症的瘤基因.
- 通过FOXM1促进致癌的精确机制和潜在的治疗策略尚未完全阐明.
研究的目的:
- 确定和描述一个涉及FOXM1及其含有1 (DEPDC1) 的目标基因DEP域的调控轴.
- 研究肝细胞癌中FOXM1/DEPDC1轴的生物功能和临床意义.
- 探索通过免疫疗法准这一轴的潜力.
主要方法:
- 研究了FOXM1.1对DEPDC1的转录调节.
- 评估了FOXM1和DEPDC1之间的相互作用,包括对核转位和转录活性的影响.
- 在细胞培养和小鼠肝细胞癌模型中利用基因沉默技术 (FOXM1敲击,DEPDC1沉默).
- 分析了来自人类肝细胞癌样本的临床数据,以确定FOXM1/DEPDC1表达和患者结果之间的相关性.
- 采用生物信息分析来识别T细胞表位和开发的T细胞受体 (TCR) 工程T细胞以准FOXM1和DEPDC1.
主要成果:
- FOXM1直接诱导DEPDC1的表达.
- DEPDC1增强FOXM1的核转位和转录活动,形成一个积极的反循环.
- FOXM1/DEPDC1轴对癌细胞扩散和瘤生长至关重要,DEPDC1从FOXM1敲击中拯救生长抑制.
- 沉默DEPDC1显著减少瘤生长在肝细胞癌的小鼠模型.
- 福克斯M1/DEPDC1轴的高表达与人类肝细胞癌患者的不良临床结果相关.
- 针对FOXM1表位 (FOXM1262-270) 和DEPDC1表位 (DEPDC1294-302) 的TCR工程T细胞在体外有效地根除了瘤细胞.
结论:
- 调节FOXM1/DEPDC1轴在肝癌发生过程中起着至关重要的作用.
- 这一轴代表了肝细胞癌的重要治疗点.
- 针对FOXM1或DEPDC1的TCR工程T细胞疗法是治疗肝细胞癌的可行策略.
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