METTL3甲基化诱导内源逆元素转录的衰变,以促进瘤的免疫逃避
Xiaowei She1, Jingqin Lan2, Haokun Zhang3
1Tongji Hospital, Tongji Medical College Wuhan, Hubei China.
Cancer research
|March 5, 2026
概括
在K513中对METTL3 (甲基转移酶类似的3) 的甲基化对结直肠癌的进展至关重要. 针对这种途径的疗法,结合免疫检查点封锁,显示出治疗CRC的希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 结肠直肠癌 (CRC) 的复发和进展仍然是重要的临床问题.
- 瘤微环境与恶性细胞的交叉声会促进复发.
- 了解这些机制是开发更好的CRC疗法的关键.
研究的目的:
- 确定驱动CRC进展和复发的关键分子修饰.
- 阐明METTL3甲基化在瘤免疫微环境中的机械作用.
- 探索针对已识别的途径的新型治疗策略.
主要方法:
- 在METTL3上确定K513二甲基化作为CRC中的关键修改.
- 确定的SETD1A催化了METTL3 K513甲基化,增强了RNA m6A的沉积.
- 研究了由甲诱导的E2F4/SETD1A/METTL3轴.
主要成果:
- METTL3甲基化增强了与SAM的结合,增加了RNA m6A沉积.
- 甲基化抑制了METTL3的反元素,损害了I型干扰素的反应,并促进了免疫逃避.
- 向E2F4或METTL3甲基化与免疫检查点阻塞协同作用,以抑制瘤生长.
结论:
- 发现了一种依赖甲基化的机制,调节CRC中的瘤免疫微环境.
- METTL3 K513甲基化是CRC进展和免疫逃避的驱动因素.
- 针对E2F4/SETD1A/METTL3轴为CRC提供了一个潜在的治疗策略.
相关概念视频
Non-LTR Retrotransposons
13.6K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.6K
MicroRNAs
24.4K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.4K
MicroRNAs
4.2K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.2K
Abnormal 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
Mechanisms of Retrovirus-induced Cancers
7.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
7.1K
Replicative Cell Senescence
4.5K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.5K


