表观遗传向克服头部和部癌症中的放射电阻
Iñaki Schniewind1,2,3, Maria José Besso4, Sebastian Klicker1
1National Center for Tumor Diseases (NCT), Faculty of Medicine, University Hospital Carl Gustav Carus, Dresden University of Technology, 01307 Dresden, Germany.
Cancers
|February 24, 2024
概括
针对UTX (KDM6A) 等表观遗传调节剂可以预防头癌的辐射抵抗. 这种方法可以使癌症干细胞 (CSC) 对放射治疗敏感,从而改善患者的治疗结果.
科学领域:
- 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.
- 癌症干细胞生物学
背景情况:
- 头部和部状细胞癌 (HNSCC) 的辐射敏感性取决于具有干状特征的癌症干细胞 (CSC).
- 辐射可以丰富抗辐射的CSC,由动态细胞可塑性驱动.
- 表观遗传机制,包括DNA和基因素甲基化,调节基因表达和细胞可塑性.
研究的目的:
- 为了研究表观遗传变化驱动辐射诱导的可塑性在HNSCC.
- 确定能防止放射电阻并使HNSCC对放射治疗敏感的表观遗传点.
- 为了评估向色素脱甲基酶的预后和治疗潜力.
主要方法:
- 对抗辐射的DNA甲基组和代谢物概况与父母HNSCC细胞系和CSCs的比较分析.
- 对表观遗传酶抑制剂的查与照射相结合.
- 对克隆基因生存,球体形成和DNA修复能力的测试.
- 在患者HNSCC组织样本中分析KDM6A和KDM6B表达.
主要成果:
- 组织素脱甲基酶抑制剂GSK-J1,向UTX (KDM6A) 和JMJD3 (KDM6B),增加了H3K27的三甲基化和基因沉默.
- 通过siRNA介导的KDM6A和KDM6B对辐射敏感的HNSCC细胞系的淘汰.
- 高KDM6A表达与治疗放射/化疗的HNSCC患者改善的局部区域控制相关.
- 高KDM6B表达与总生存率降低有关.
结论:
- 表观遗传变化在HNSCC的放射电阻和细胞可塑性中起着至关重要的作用.
- UTX (KDM6A) 被确定为接受放射治疗的HNSCC患者的潜在预后和治疗标.
- 向表观遗传机制提供了一个有希望的策略,以克服HNSCC中的放射电阻.
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