通过FFAR4激活,通过阻断呼吸链复杂组合和相关的线粒体代谢,抑制肺腺癌
Zhe Wang1, Jinyou Li2, LongFei Wang3
1Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Cellular & molecular biology letters
|January 19, 2024
概括
自由脂肪酸受体4 (FFAR4) 在肺腺癌 (LUAD) 中降低,与生存率较差相关. FFAR4的激活抑制了LUAD细胞的生长,并改变了新陈代谢,这表明它是诊断和治疗的目标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- 肺腺癌 (LUAD) 的死亡率高,预后不佳.
- 自由脂肪酸受体 (FFARs) 可能在LUAD中将遗传和饮食因素联系起来.
- FFAR4是食脂肪酸的主要受体.
研究的目的:
- 调查FFAR4表达和LUAD特征之间的相关性.
- 探索LUAD中FFAR4的潜在机制.
- 评估FFAR4作为LUAD潜在的诊断和治疗点.
主要方法:
- 在LUAD组织中评估FFAR4表达.
- 与患者整体存活时间 (OS) 相关联的FFAR4水平.
- 使用的接收器运行特征 (ROC) 曲线分析用于诊断价值.
- 在功能性试验中使用FFAR4特异性激动剂 (TUG891).
- 在A549细胞中测量了氧气消耗率 (OCR) 和细胞外酸化率 (ECAR).
- 研究了FFAR4对线粒体呼吸链复合体和酸盐-酸盐穿物的影响.
主要成果:
- 在LUAD中,FFAR4的表达下降.
- 较高的FFAR4水平与改善的生存状况正相关 (P < 0.01).
- FFAR4表达显示出显著的诊断价值 (AUC = 0.933).
- TUG891抑制了LUAD细胞的增殖,并诱导了细胞循环停止.
- 在A549细胞中,FFAR4激活降低了OCR,增加了ECAR.
- FFAR4激活会损害线粒体功能和NAD+/NADH过渡.
结论:
- 在LUAD中,FFAR4在线粒体代谢的负调节中发挥作用.
- FFAR4的激活抑制了LUAD的进展.
- FFAR4是用于LUAD诊断和治疗的潜在治疗点.
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