METTL14通过通过单细胞和机器学习分析识别的m6A-修饰的YWHAH调节鼻癌微环境
Zuming Liang1,2, Zhihao Zhou1, Jing Wang1
1Laboratory Animal Management Center, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Frontiers in immunology
|February 18, 2026
概括
N6-甲基氨酸 (m6A) 甲基化影响鼻癌 (NPC) 的进展. 这项研究确定YWHAH是关键的m6A调节基因,影响NPC免疫微环境和TNF-α信号传递.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 鼻癌 (NPC) 是一种在中国南部普遍存在的侵袭性癌症.
- 越来越多地认识到N6-甲基氨酸 (m6A) 甲基化对NPC进展的作用.
- 在NPC中的细胞因子活性有助于免疫抑制和免疫逃避.
研究的目的:
- 研究m6A甲基化在NPC免疫微环境中的作用.
- 为了确定关键的m6A调节基因参与NPC病变发生.
- 阐明将m6A,细胞因子和NPC进展联系起来的调节机制.
主要方法:
- 集成的单细胞和批量RNA测序与MeRIP-seq.
- 采用高维分析,包括hdWGCNA和细胞间通信.
- 利用机器学习和免疫透分析来识别更多的A调节基因.
- 通过NPC细胞中的基因淘汰/过度表达来验证的发现.
主要成果:
- 鉴定出B细胞是TNF通路的主要发送者.
- YWHAH成为一个关键的TNF相关的,m6A调节的基因,在特定的免疫和上皮细胞中表达升高.
- METTL14缺乏增加了YWHAH转录的丰富性和稳定性,而TNF-α刺激增强了YWHAH表达.
- 由于YWHAH的淘汰,NPC细胞迁移受损,IL-6/IL-8表达发生改变.
结论:
- 确定YWHAH是一种METTL14受调节的基因,对NPC免疫微环境至关重要.
- 增加YWHAH表达与NPC中的免疫平衡调节有关.
- 在NPC中建议TNF-α,YWHAH和METTL14之间的潜在调节联系.
相关概念视频
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...