跨癌症的全转录组RNA稳定性揭示了治疗脆弱性
Yang Tong1, Yuting Wang2, Gerui Liu3
1Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Journal of molecular biology
|December 10, 2025
概括
由RNA衰变控制的RNA稳定性,在癌症中起着至关重要的作用. 这项研究揭示了RNA稳定性概况可以预测药物反应,并在癌症精确瘤学中确定新的治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
背景情况:
- 稳定状态mRNA水平取决于转录和降解.
- 在癌症中RNA稳定性的作用尚不清楚.
- 转录后调节是癌症发展的关键.
研究的目的:
- 在各种癌症类型中调查RNA衰变动态.
- 根据RNA稳定性确定分子亚型.
- 探索RNA结合蛋白 (RBPs) 和微RNA (miRNAs) 在癌症RNA稳定性中的作用.
主要方法:
- 来自癌症细胞系百科全书的RNA-seq数据的系统分析.
- 对全转录组RNA稳定性概况的推断.
- 对RBP,miRNA和体突变的综合分析.
- 机器学习模型用于预测药物敏感性.
主要成果:
- 通过RNA稳定性确定了不同的癌症亚型.
- RBPs (例如,SNRPA,RBMX) 和miRNAs是RNA稳定性和癌细胞存活的关键调节剂.
- 影响miRNA结合部位的体质突变破坏了RNA衰变.
- RNA稳定性概况预测了对24种抗癌药物的敏感性.
结论:
- RNA稳定性是癌症中关键的调节层.
- RNA稳定性概况对分子分层有影响.
- 在精密瘤学中,RBP是预测治疗反应的潜在生物标志物.
相关概念视频
01:53RNA Stability
35.6K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
35.6K
02:51mRNA Stability and Gene Expression
6.5K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
6.5K
02:51mRNA Stability and Gene Expression
3.4K
3.4K
01:22MicroRNAs
3.7K
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...
3.7K
01:22MicroRNAs
23.8K
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...
23.8K
01:29Translational Regulation
507
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
507