通过YBX1/RAC3轴,SETD8抑制了尤文肉瘤的亡和铁亡
Huimou Chen1, Jing Hu2,3, Xilin Xiong4
1Department of Oncology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiang Road, Guangzhou, 510120, China.
Cell death & disease
|July 10, 2024
概括
在尤文肉瘤 (ES) 中升高调节的蛋白质SETD8,通过抑制细胞死亡途径来驱动瘤生长. 准SETD8为这种侵袭性儿科癌症提供了一个有前途的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 尤文肉瘤 (ES) 是一种具有攻击性的儿科癌症,结果不佳,特别是在复发/耐药病例中.
- 目前的治疗方法缺乏有效性,这凸显了对新型治疗点的需求.
- SETD8 (氨酸甲基转移酶5A) 涉及各种癌症,但其在ES中的作用尚不清楚.
研究的目的:
- 研究SETD8在ES病变发生中的作用及其作为治疗点的潜力.
- 阐明SETD8影响ES细胞死亡和瘤发生的分子机制.
主要方法:
- 使用SETD8抑制剂 (UNC0379) 和ES细胞中的RNA干扰的体外研究.
- 对亡和铁亡的分析.
- 用于分子分析的RNA测序 (RNA-seq) 和质谱.
- 在体内研究使用裸体老鼠异种移植模型.
主要成果:
- 在ES中SETD8是上调调节的,并且与患者的不良结果有关.
- 在ES细胞中,SETD8敲击诱导了亡和铁亡,并在体内抑制了瘤生长.
- 通过YBX1/RAC3轴,SETD8促进ES瘤发生,调节YBX1核转位和RAC3转录.
结论:
- 通过抑制亡和铁亡,SETD8在ES细胞存活和瘤发生中发挥着关键作用.
- YBX1/RAC3信号通路是SETD8在ES中的致癌功能中介的关键机制.
- 在Ewing瘤中,SETD8是临床干预的潜在治疗点.
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