以NSUN2为媒介的R循环稳定是膀癌进展和西斯普拉丁敏感性的关键驱动因素
Yuqing Wu1, Yufan Ying1, Fenghao Zhang2
1Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Cancer letters
|December 28, 2024
概括
这项研究表明,膀癌 (BCa) 中R环升高被NSUN2稳定,促进癌症的进展. 准NSUN2使瘤对思素敏感,并损害DNA修复,提供新的治疗途径.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 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:
- R环对于基因组稳定性和基因表达调节至关重要.
- R环的失调与各种癌症有关,包括膀癌 (BCa).
- 在R循环动力学和BCa中5-甲基细胞因子 (m5C) 甲基转移酶NSUN2的作用尚不清楚.
研究的目的:
- 研究膀癌细胞中NSUN2和R环之间的相互作用.
- 阐明NSUN2在BCa中转录调节和DNA损伤修复中的作用.
- 为了确定膀癌治疗的潜在治疗点.
主要方法:
- 对BCa细胞中的R循环水平与正常尿细胞的分析.
- 研究NSUN2与R环的相互作用及其催化活性依赖性的研究.
- 评估NSUN2对EZH2对PRDM11基因促进体的招募.
- 评估NSUN2对瘤生长,DNA损伤和同源重组修复的淘汰效应.
主要成果:
- 与正常细胞相比,BCa细胞中观察到较高的R环水平.
- NSUN2通过其m5C催化活性结合并稳定R循环.
- NSUN2招募EZH2以表观遗传沉默瘤抑制剂PRDM11,促进BCa的进展.
- NSUN2 knockdown使BCa对西斯普拉丁敏感,减少瘤生长,增加DNA损伤,并损害MRE11的招募,阻碍同源重组修复.
结论:
- NSUN2是膀癌中R环的关键调节者,通过表观遗传沉默PRDM11.1促进瘤发生.
- NSUN2在DNA损伤修复中发挥着关键作用,特别是同源重组.
- 准NSUN2为膀癌提供了一个有前途的治疗策略,可能会提高对诸如思柏之类的化疗的敏感性.
关键词:
膀癌是一种癌症.H3K27me3 在线阅读同类的重组组合.M(5)C5)C5)C5)C5)C5)C5)C5)C5)C5)C5)C5)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)C)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)D)在MRE11中,MRE11是MRE11中的一个.在NSUN2中,NSUN2是NSUN2.在R-Loop中使用.
相关概念视频
02:56Treatment Resistant Cancers
3.2K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
01:20The Retinoblastoma Gene
4.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
02:55The Nucleolus
8.6K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.6K
02:39lncRNA - Long Non-coding RNAs
8.4K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.4K