在胃癌中,JMJD3上调调节ALOX5以驱动恶性瘤和并发性铁死敏感性
Gege Shu1, Jiaoyang Yang2, Huifang Hu3
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. sggshu@163.com.
Cell death & disease
|November 3, 2025
概括
JMJD3 (KDM6B) 通过改变基因组修饰,促进胃癌 (GC) 化学抵抗和干性. 准JMJD3和使用铁灭菌诱导剂可能提供新的GC治疗策略.
科学领域:
- 在瘤学瘤学.
- 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.
背景情况:
- 化疗耐药性是胃癌 (GC) 治疗的一个主要挑战.
- 癌症干部的增加有助于GC的化疗抵抗.
- 氧化 (OXA) 是对GC的关键一线化疗剂.
研究的目的:
- 调查JMJD3 (编码为KDM6B) 在GC化学抵抗和干性中的作用.
- 阐明JMJD3影响GC恶性瘤的分子机制.
- 探索JMJD3作为克服GC化学抵抗的潜在治疗标.
主要方法:
- 在GC组织和患者衍生异种移植 (PDX) 模型中评估了JMJD3表达.
- 在GC细胞中操纵了JMJD3表达 (过度表达和淘汰).
- 在ALOX5促进体上分析了组素修饰 (H3K27me3).
- 利用Kdm6b删除的小鼠模型来研究瘤发生.
- 研究了JMJD3对GC细胞中铁灭敏感性的影响.
主要成果:
- 在GC组织和耐化学反应的PDX模型中,JMJD3的表达很高.
- 过度表达JMJD3增强了GC细胞干细胞和化学抵抗性;敲除具有相反的效果.
- 在ALOX5促进体上,JMJD3降低了H3K27me3,导致其转录激活.
- 胃上皮细胞特异性的Kdm6b删除减少了MNU诱导的瘤发生.
- 增加的JMJD3/ALOX5功能使GC细胞对ferroptosis诱导物的敏感.
结论:
- JMJD3通过促进茎状性和调节铁灭症敏感性,在GC化学抵抗中发挥着关键作用.
- 向JMJD3为克服GC化疗耐药性提供了一个新的治疗策略.
- 铁致死诱导剂在与针对JMJD3的疗法相结合时,可以作为一种有前途的GC辅助治疗.
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