通过MAPK信号介导的RFNG酸化和核转移抑制了oxaliplatin诱导的亡和铁亡
Yuqin Di1,2, Xiang Zhang2, Xiangqiong Wen2
1Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 9, 2024
概括
减少RFNG蛋白质使结肠直肠癌细胞对酸化疗敏感. 这是通过阻止RFNG来实现的.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌细胞生物学 癌细胞生物学
背景情况:
- 化疗耐药性是治疗结直肠癌 (CRC) 的重要障碍.
- 需要新的策略来提高化疗在CRC治疗中的疗效.
研究的目的:
- 调查边缘家族在结直肠癌化学疗法耐药性中的作用.
- 阐明RFNG影响氧沙抗性的分子机制.
主要方法:
- 对边缘家族进行查,以查看其是否参与化学疗法耐药性.
- 研究化RFNG (pS255) 与核进口物的相互作用.
- 分析RFNG操纵对p53酸化和下游基因表达的影响.
- 在体外和体内使用RFNG突变体和患者衍生的异种移植模型评估对西的反应.
主要成果:
- 消耗了RFNG对氧沙敏感的结直肠癌细胞.
- 化RFNG (pS255) 通过干扰CHK2结合,降低亡和铁亡来抑制p53化.
- 一种缺乏的RFNG突变体 (S225A) 显示出亡和铁亡的增加,对酸反应良好.
- 在患者衍生异种移植模型中,低RFNG pS255水平与氧化敏感性相关.
结论:
- 在结直肠癌中,RFNG充当氧沙素耐药性的调解者.
- 通过RFNG调解的MAPK和p53信号通路之间的交叉对抗对于化学抵抗至关重要.
- 向RFNG酸化或表达可能提供一种治疗策略,以克服CRC患者的氧化抗性.
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