KCNJ15抑制化学诱导的肺癌发生和通过GNB1介导的Hippo路径的进展
Hong-Qiang Chen1, Na Wang2, Yong Zeng1
1Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.
通道KCNJ15在肺癌中起到瘤抑制作用. 它的低表达,由于DNA甲基化,通过影响Hippo-YAP通路促进癌症生长和转移.
科学领域:
- 环境表观遗传学环境表观遗传学
- 分子瘤学分子瘤学
- 致癌的机制 致癌机制
背景情况:
- 多环芳 (PAH) 是环境致癌物,与肺癌有关.
- 在PAH诱导的肺癌发生过程中的表观遗传机制尚未完全理解.
- KCNJ15被确定为肺癌发生的潜在表观遗传调节者.
研究的目的:
- 研究KCNJ15在肺癌发生中的作用.
- 阐明KCNJ15的表达调节,功能和分子机制.
- 确定KCNJ15在Hippo-YAP信号通路中的参与.
主要方法:
- 数据库分析数据库分析
- 恶性转化细胞模型 (HBE细胞)
- 异种移植瘤模型
- 对DNA甲基化分析进行分析.
- 基因表达和淘汰研究.
- 蛋白质与蛋白质相互作用的测试.
主要成果:
- 在肺癌发生和进展中,KCNJ15的下调显著.
- DNA甲基化与转化细胞中的KCNJ15表达相反相关.
- 高KCNJ15表达预测了更好的患者存活率.
- 过度表达KCNJ15抑制肺癌细胞的生长,入侵和迁移在体外和体内.
- KCNJ15通过YAP的酸化和表达来调节Hippo-YAP通路.
- KCNJ15与GNB1相互作用,GNB1调节其对Hippo通路的影响.
结论:
- 在化学诱导的肺癌发生过程中,KCNJ15作为表观遗传瘤抑制剂起作用.
- KCNJ15通过GNB1-介导的Hippo-YAP通路调节细胞增殖,入侵和迁移.
- 这项研究提供了有关癌症发生过程中环境污染物的表观遗传调节的见解.
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