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在FOXP4中Cis-regulatory的改变调节由慢性酒精暴露引起的食道癌易感性
Siyuan Niu1, Jialing Ma1, Shasha Liu1
1Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cancer research
|April 14, 2025
概括
长期使用酒精会增加食道状细胞癌 (ESCC) 的风险. 一种特定的FOXP4基因变异 (rs10223516) 与酒精相互作用,通过改变基因表达,显著提高ESCC易感性和瘤生长.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 环境健康 环境健康
背景情况:
- 慢性饮酒是食道状细胞癌 (ESCC) 的已知危险因素.
- 了解将酒精暴露与ESCC联系在一起的遗传和表观遗传机制对于预防和早期检测至关重要.
研究的目的:
- 识别参与食道癌发生的酒精反应基因和 cis 调节元件 (CREs).
- 研究特定遗传变异在与酒精相关的ESCC易感性中的作用.
主要方法:
- 利用小鼠模型在慢性乙醇暴露下研究食道上皮.
- 在人类ESCC中构建了一个全面的CRE基因图,并进行了一项大规模的病例控制研究.
- 进行功能测试,ChIP-seq和RNA-seq以验证基因变异效应.
主要成果:
- 鉴定了222个与ESCC进展相关的酒精反应基因,丰富了增殖和瘤发生路径.
- 在FOXP4基因中发现了一种增强剂变异 (rs10223516),通过基因-酒精相互作用与ESCC风险相关.
- rs10223516 T等位基因增加了FOXP4的表达和活性,导致饮酒者患ESCC风险更高,并通过激活CYP26B1和MYC促进瘤生长.
结论:
- 基因与环境的相互作用,特别是酒精消费和表观遗传变化,在食道瘤发生中起着重要作用.
- FOXP4 变异 rs10223516 是ESCC 对酒精消费者的风险评估的潜在生物标志物.
- 这些发现为ESCC的检测和预防策略提供了新的目标.
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