针对PHF8/YY1轴通过调节ROS抑制癌细胞生长
Xiao-Nan Wu1,2, Jia-Yuan Li1,2, Qi He1,2
1State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361102, China.
概括
蛋白脱甲基酶PHF8通过抑制电子运输链 (ETC) 基因驱动癌症. 使用iPHF8准PHF8通过恢复ETC基因表达和减少线粒体ROS来抑制癌细胞生长和瘤发育.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 线粒体的新陈代谢
背景情况:
- 高水平的线粒体活性氧物种 (mROS) 与癌症的发展有关.
- 电子输送链 (ETC) 严格调节mROS,但癌症中ETC基因转录的表观遗传控制尚未完全理解.
研究的目的:
- 研究控制癌症ETC基因转录的表观遗传机制.
- 为了确定癌症治疗的新型治疗点.
主要方法:
- 在各种癌症类型中分析PHF8的过度表达.
- 研究PHF8在调节YY1甲基化和ETC基因表达中的作用.
- 在癌细胞系和异种移植模型中使用iPHF8对PHF8进行药理抑制.
- 评估mROS的产生,细胞生长和瘤抑制.
主要成果:
- 在癌症中,PHF8过度表达,与ETC基因表达有负相关性.
- PHF8通过去甲基化转录因子YY1作为共抑制剂,抑制核编码ETC基因.
- 药理上抑制PHF8 (iPHF8) 有效地逆转YY1甲基化,恢复ETC基因转录,减少mROS,并抑制癌细胞生长.
- 在体内异种移植模型中,iPHF8显示出强大且安全的瘤抑制作用.
结论:
- PHF8通过PHF8/YY1轴表观遗传调节ETC基因转录,促进mROS的产生和癌症的发展.
- 使用iPHF8准PHF8/YY1轴是治疗癌症的一个有前途的治疗策略.
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