乳酸通过调节m6A修饰介导的FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R轴来促进NSCLC中西斯普拉丁耐药性
Wei Bo1, Ning Yu2, Xiaokai Wang3
1College of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan, Huanggu District, Shenyang, Liaoning 118047, China; Pathology Department of Shenyang Medical College, Shenyang, Liaoning 110034, China.
Neoplasia (New York, N.Y.)
|January 7, 2024
概括
增加的乳酸盐通过m6A修饰通过降低FOXO3的调节促进非小细胞肺癌 (NSCLC) 中的西斯普拉丁耐药性. 这一途径涉及MAGI1-IT1,miR-664b-3p和IL6R,影响治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 在治疗非小细胞肺癌 (NSCLC) 方面,西斯普拉丁耐药性是一个重大挑战.
- 在抗西斯普拉丁的NSCLC细胞中观察到乳酸盐水平升高,这表明它在抵抗机制中起着作用.
研究的目的:
- 研究乳酸酸通过哪些生物机制影响NSCLC中西斯普拉丁耐药性的生物学机制.
- 阐明涉及乳酸盐,FOXO3和相关因子在NSCLC西斯普拉丁耐药性的分子途径.
主要方法:
- 建立抗西斯普拉丁的NSCLC细胞系和体内模型.
- 评估细胞活力,增殖,细胞亡和基因表达 (m6A修饰,RIP,ChIP,露西法酶试验).
- 测量乳酸水平和基因相互作用的分析.
主要成果:
- 乳酸盐治疗增加了NSCLC细胞活力和瘤生长,加剧了西斯普拉丁耐药性.
- 乳酸通过YTHDF2介导的m6A修饰来降低FOXO3的调节,这通过转录减少了MAGI1-IT1的表达.
- 确定了FOXO3/MAGI1-IT1/miR-664b-3p/IL6R轴作为乳酸诱导的西斯普拉丁耐药性的关键媒介.
结论:
- 乳酸盐通过FOXO3的YTHDF2介导的m6A修饰促进NSCLC的抗西斯普拉丁抵抗,影响FOXO3/MAGI1-IT1/miR-664b-3p/IL6R信号轴.
- 针对这种乳酸驱动的途径提供了潜在的治疗策略,以克服NSCLC中西斯普拉丁耐药性.
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