一个G-四倍体结合复合体通过双重准线粒体和核G4丰富基因组诱导癌症线粒体功能障碍
Keli Kuang1, Chunyan Li1, Fatlinda Maksut2,3
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, 610041, Chengdu, China.
Journal of biomedical science
|May 14, 2024
概括
这项研究揭示了一种复合物,Pt-ttpy,通过影响核和线粒体基因组,有效地准癌症线粒体. 它在不增加活性氧物种 (ROS) 的情况下破坏线粒体功能,提供了一个有前途的新型癌症疗法.
科学领域:
- 生物化学 生物化学
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
背景情况:
- 在核和线粒体基因组中越来越多地识别了G-四重复基因组 (G4) 结构,并在癌症中发挥作用.
- 利用G4结构的向疗法正在出现,但它们对基因组和线粒体功能的影响仍然不清楚.
研究的目的:
- 研究G4结合(II) 复合体Pt-ttpy对癌细胞线粒体的机制和治疗作用.
- 探索Pt-ttpy对核和线粒体基因组的影响及其对线粒体功能的影响.
主要方法:
- 使用了体外和体内模型的技术,包括ICP-MS,PCR,Western blotting,共聚焦显微镜,细胞外流量分析,JC1和Annexin V测定,流细胞计和高含量显微镜.
- 采用RNA-seq,Chip-seq和CUT-RUN测试来分析Pt-ttpy对核编码线粒体基因的影响.
主要成果:
- Pt-ttpy优先积聚在线粒体中,并诱导线粒体DNA (mtDNA) 删除,拷贝减少和转录抑制,阻碍线粒体蛋白转化.
- 线粒体功能障碍在没有诱导活性氧物种 (ROS) 的情况下被观察到.
- 发现pt-ttpy通过干扰与转录因子结合G4丰富的促进子区域来损害核编码的线粒体核糖体基因的转录.
结论:
- Pt-ttpy在核和线粒体G4丰富基因组上表现出双重作用,有效向癌症线粒体.
- 这种G4结合复合物为基于的G4向癌症治疗提供了一种更安全,更有效的方法,其副作用比西斯更少.
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