在膀癌中,NSUN2介导的SOCS3mRNA的m5C修饰调节了巨细胞两极分化
Yi Tang1,2,3, Xinpei Deng1,2,3, Yanjun Wang1,2,3
1Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cell death & disease
|December 7, 2025
概括
5甲基氨酸 (m5C) 甲基化调节膀癌中的巨细胞极化. NSUN2甲基化SOCS3mRNA,通过JAK2/STAT3通路促进M2巨细胞的两极分化,并抑制M1两极分化.
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:
- 瘤相关巨细胞 (TAMs) 影响癌症进展,M1和M2亚型表现出相反的作用.
- 虽然N6-腺素 (m6A) 甲基化在巨细胞两极分化中的作用已知,但5-甲基素 (m5C) 甲基化的功能尚不清楚.
- 在膀癌瘤微环境 (TME) 中,M2巨细胞普遍存在.
研究的目的:
- 调查m5C甲基化在调节膀癌中巨细胞极化中的作用.
- 为了识别关键的m5C调节者参与M2巨分化.
- 阐明m5C甲基化影响巨细胞表型的分子机制.
主要方法:
- 光激活细胞分类 (FACS) 和免疫光 (IF) 以确定M2巨细胞的存在.
- 定量PCR (qPCR) 和全转录组再测序用于选m5C调节器并确定下游目标.
- RNA免疫沉 (RIP) 以确认RNA甲基化位点并评估mRNA稳定性和核出口.
主要成果:
- 证实M2巨细胞是膀癌TME中占主导地位的亚型.
- NOP2/Sun RNA甲基转移酶家族成员2 (NSUN2) 被确定为M2巨细胞中显著上调的m5C甲基酶.
- 发现NSUN2会甲基化SOCS3mRNA,降低其稳定性和核出口,从而激活JAK2/STAT3通路并促进M2极化,同时抑制M1极化.
结论:
- SOCS3 mRNA的NSUN2介导的m5C甲基化是驱动膀癌中M2巨分化的一个关键机制.
- 这个过程涉及YBX1阅读器和TET2擦拭器,突出显示了一个复杂的监管网络.
- 通过调节TME,准NSUN2或SOCS3通路可能为膀癌提供新的治疗策略.
更多相关视频
06:57Author Spotlight: Decoding RNA Methylation's Role in Pancreatic Cancer - A Single-Base Resolution Study
Published on: July 7, 2023
1.5K
10:43Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
32.0K
相关概念视频
02:23Abnormal Proliferation
5.1K
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...
5.1K
02:17The Tumor Microenvironment
7.6K
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...
7.6K
01:15Receptor Downregulation in MVBs
2.7K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.7K