协调的DNA甲基转移酶3A和甲基转移酶类型的7A活动通过迪斯科丁域受体1信号重新编程瘤微环境
Zhengyang Bai1, Dan Yang1, Jiayi Li2
1The First Clinical Medical School of Ningxia Medical University (General Hospital of Ningxia Medical University), Yinchuan 750004, China.
Cancer biology & medicine
|February 17, 2026
概括
表观遗传调节者DNMT3A和METTL7A通过控制DDR1/STAT3/CXCL5轴来驱动乳腺癌复发,促进免疫逃避和瘤生长. 沉默DDR1扭转了这些影响,提供了新的治疗点.
科学领域:
- 分子瘤学分子瘤学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症免疫学 癌症免疫学
背景情况:
- 乳腺癌复发显著影响患者的生存率.
- 瘤微环境调节T细胞 (Tregs) 促进免疫逃避和转移.
- 表观遗传调节者DNMT3A和METTL7A与癌症进展有关.
研究的目的:
- 研究DNMT3A和METTL7A如何通过DDR1/STAT3/CXCL5轴调节Treg透.
- 确定这个轴在乳腺癌复发和预后中的作用.
主要方法:
- RNA测序确定了差异表达的基因.
- 机器学习算法 (LASSO,SVM-RFE,ElasticNet) 确定了DDR1作为一个关键基因.
- 验证涉及RT-qPCR,西斑,甲基化特异性PCR,MeRIP-qPCR,Co-IP,功能测定和异种移植模型.
主要成果:
- DNMT3A通过DNA甲基化提高了DDR1的调节;METTL7A通过m6A修改增强了DDR1mRNA的稳定性.
- 同调节激活了DDR1/STAT3/CXCL5轴,增加了癌细胞的增殖,迁移和入侵.
- 在体内,CXCL5分泌促进了Treg透和瘤生长;DDR1沉默逆转了这些效应.
结论:
- DNMT3A和METTL7A通过DNA/m6A甲基化合作调节DDR1,推动Treg介导的免疫抑制和复发.
- DDR1/STAT3/CXCL5轴对乳腺癌复发至关重要.
- 这些发现为乳腺癌预后和治疗提供了新的见解和潜在的治疗点.
相关概念视频
02:23Abnormal Proliferation
5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
02:17The Tumor Microenvironment
7.9K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.9K
02:23Master Transcription Regulators
7.9K
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...
7.9K
01:37Epigenetic Regulation
3.9K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.9K
01:46Epigenetic Regulation
34.0K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.0K
03:03mTOR Signaling and Cancer Progression
4.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.9K