在癌细胞中相互排斥的表达的分析确定了以前未知的基因间调节范式
Ling Tang1,2,3, Yuzhe Hu1,2, Chao Wang1,2
1Department of Immunology, NHC Key Laboratory of Medical Immunology (Peking University), Medicine Innovation Center for Fundamental Research on Major Immunology-Related Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
The FEBS journal
|April 5, 2025
概括
研究人员发现了一种新方法,在癌细胞中找到相互排斥的基因表达模式. 他们发现,醇甲基转移酶1B (METTL7B) 负面调节PD-L1表达,影响免疫反应.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 基因表达的相互排斥是一个研究不足的现象.
- 基因表达可塑性分析提供了一种识别高度可塑性基因 (HPG) 的方法.
研究的目的:
- 在人类癌症细胞系中量化测量基因表达可塑性.
- 为了确定相互排斥的基因表达模式和对.
- 调查METTL7B和PD-L1.1之间的监管关系.
主要方法:
- 对24个人类癌细胞系中的19961个蛋白质编码基因的基因表达可塑性的分析.
- 对比不同的方法 (虚拟排序,等号相似性,皮尔森,斯皮尔曼) 来识别相互排斥.
- 使用细胞共同培养和敲击实验进行实验验证.
主要成果:
- 虚拟排序和等号相似性被确定为检测相互排斥的合适方法.
- 在每个细胞类型中都发现了相互排斥的基因对.
- 发现二醇甲基转移酶1B (METTL7B) 和CD274分子 (PD-L1) 相互排他性表达.
- 已经证明METTL7B可以负面调节PD-L1表达,涉及JAK/STAT3通路.
- 在共同培养系统中,METTL7B knockdown抑制了IL-2分泌,而这种分泌被抗PD-L1抗体阻断了.
结论:
- 已经建立了一种分析表达式相互排斥的强有力的方法.
- 提出了一种涉及癌细胞中METTL7B和PD-L1的新型基因间调节范式.
- 这一发现对了解癌症中的免疫调节有意义.
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