尼古丁衍生的NNK通过激活TMUB1/AKT通路以METTL14/YTHDF2-介导的m6A方式促进CRC进展
Min Jiang1, Jingyi Han2, Qun Ma2
1School of Public Health, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Journal of hazardous materials
|February 11, 2024
概括
吸烟会促进结直肠癌的进展. 作为一种致癌物质的NNK通过N6-氨酸甲基化对TMUB1进行上调,从而导致侵入和转移,这表明TMUB1是治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 结肠直肠癌 (CRC) 受香烟吸烟的影响很大,但驱动其进展的分子机制尚未完全理解.
- 研究吸烟和CRC之间的联系揭示了与较大的瘤大小,差异化和侵入性增加的相关性.
研究的目的:
- 阐明吸烟,特别是NNK促进结直肠癌进展的分子机制.
- 确定吸烟相关结直肠癌的潜在治疗和预后标.
主要方法:
- 分析了662名结肠直肠癌患者的数据.
- 在体内和体外使用NNK的实验.
- 甲基化RNA免疫沉降和转录组测序.
- 研究TMUB1,METTL14和YTHDF2的相互作用.
主要成果:
- NNK显著促进结直肠癌的进展.
- 通过METTL14/YTHDF2-介导的N6-氨酸甲基化,NNK通过TMUB1表达进行上调.
- 升高的TMUB1水平与CRC患者的侵袭,转移和死亡风险增加相关.
- TMUB1促进AKT的无处不在,推动恶性扩散和转移.
结论:
- 该研究确定了一种涉及NNK,N6-氨酸甲基化,TMUB1和AKT在结直肠癌进展中的全方位化的新型分子途径.
- 通过METTL14/YTHDF2-介导甲基化向TMUB1表达,为结直肠癌吸烟者提供了潜在的治疗策略.
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