SF3B3调节的mTOR替代拼接促进结直肠癌的进展和转移
Tong Xu1, Xichuan Li2, Wennan Zhao1
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
Journal of experimental & clinical cancer research : CR
|April 26, 2024
概括
SF3B3通过改变mTOR拼接和脂质生成来促进结直肠癌 (CRC) 的进展和转移. 抑制SF3B3为CRC治疗提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 异常替代拼接 (AS) 在结直肠癌 (CRC) 发展中很常见.
- 一种拼接因子SF3B3对于拼接体组装至关重要.
- 此前尚不清楚SF3B3在CRC病变发生中的特定作用.
研究的目的:
- 研究SF3B3在结直肠癌进展和转移中的作用.
- 阐明SF3B3影响CRC的分子机制.
- 评估SF3B3作为CRC的潜在治疗点.
主要方法:
- 在CRC中使用公开数据集,IHC,qRT-PCR和Western blot进行SF3B3表达式分析.
- 使用CRC细胞系,异种移植,有机体和具有SF3B3调制的小鼠模型的体外和体内研究.
- RNA-seq,RNA免疫沉降和脂管学来确定分子机制.
主要成果:
- SF3B3在CRC上升调节,并与患者生存率低下有关.
- 抑制SF3B3抑制了CRC细胞的增殖和转移在体外和体内.
- SF3B3沉默导致了mTOR替代拼接,通过mTOR-SREBF1-FASN信号传递减少了脂质生成,线粒体损伤,ROS增加和亡.
- 结合SF3B3抑制和mTOR抑制剂在临床前模型中显示出协同效应.
- 在多种癌症类型中,SF3B3调节了mTOR拼接和自.
结论:
- SF3B3通过mTOR替代拼接和SREBF1-FASN介导的脂质生成促进CRC进展和转移.
- SF3B3被确定为mTOR拼接和自的关键调节者.
- SF3B3代表了结直肠癌治疗的可用药物标.
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