在结直肠癌中N1-甲基亚丁素 (m1A) 修改模式的风景
Chunhui Jiang1, Yuan Tian1, Chunjie Xu1
1Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer reports (Hoboken, N.J.)
|December 20, 2023
概括
N1-甲基氨酸 (m1A) 变化通过影响瘤免疫微环境,影响结直肠癌 (CRC) 的发展和预后. 高的m1A分数与较差的结果相关,这表明有针对性的免疫疗法的潜力.
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:
- N1-甲基氨酸 (m1A) 是一种新兴的mRNA修饰,在结直肠癌 (CRC) 发病过程中没有明确的作用.
- 在CRC中,m1A修饰模式与瘤免疫微环境 (TIME) 之间的关系在很大程度上仍未被探索.
研究的目的:
- 在CRC中全面评估m1A甲基化调节剂.
- 评估m1A修饰模式对瘤免疫微环境和CRC的预后的影响.
- 在CRC中探索m1A修饰模式的临床价值.
主要方法:
- 使用癌症基因组图谱 (TCGA) 数据库对398名CRC患者和39名健康对照人的回顾性分析.
- 使用主要组件分析开发一个m1Ascore来评估m1A修改模式.
- 确定关键的m1A相关的差异表达基因 (DEGs) 以及它们与侵袭,转移和预后的关联.
主要成果:
- 确定了12个关键的m1A相关的DEG,包括CLDN3,MUC2和CCDC85B,与CRC入侵和转移有关.
- 突出了RNA代谢和生物合成作为与免疫反应疲弱和预后不佳相关的关键过程.
- 证明,与得分较低的患者相比,高m1A得分的患者表现出较高的瘤负担和更糟糕的预后.
结论:
- 在CRC中存在多种m1A修饰模式,通过它们对TIME和免疫功能障碍的影响,显著影响预后.
- m1A的改变为CRC的发展和异质性提供了新的见解.
- 这些发现可能有助于开发针对CRC的个性化免疫疗法策略.
相关概念视频
RNA Editing
9.0K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.0K
Abnormal Proliferation
4.5K
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...
4.5K
Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K
Epigenetic Regulation
31.1K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.1K
Pre-mRNA Processing: Modification of pre-mRNA Ends
9.3K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
9.3K
MicroRNAs
3.0K
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...
3.0K


