核糖体生物发生是儿科神经母细胞瘤的治疗脆弱性
bioRxiv : the preprint server for biology
|April 8, 2025
概括
向核糖体生物发生,对癌细胞增殖至关重要,为神经母细胞瘤提供了一个新的治疗策略. 抑制这一过程和向纤维素素 (FBL) 显示有望减少瘤生长.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症治疗方法 癌症治疗方法
背景情况:
- 神经母细胞瘤是一种异质的儿科癌症,预后与年龄和阶段有关.
- 目前的治疗方法使用年龄,阶段,MYCN状态和基因组资料.
- MYC的瘤性活性依赖于核糖体生物发生,这是由于癌症过度激活而成为潜在的治疗标.
研究的目的:
- 作为神经母细胞瘤的脆弱性,研究核糖体生物发生.
- 在神经母细胞瘤模型中评估抑制核糖体生物发生的疗效.
- 在核糖体生物发生路径中识别新的治疗点.
主要方法:
- 利用IMR-32和患者衍生的神经母细胞瘤细胞系,包括一个用纤维素 (FBL) 敲击.
- 分析了细胞生长,细胞亡和细胞循环调节剂.
- 通过公开数据集和RT-qPCR评估了核糖体生物发生因子表达.
主要成果:
- RNA聚合酶I抑制 (CX-5461,BMH-21) 通过核糖体应激和p21激活抑制了增殖和诱导了亡.
- 纤维素 (FBL) 被确定为神经母细胞瘤的不良预后标志物.
- 抗击FBL降低了神经母细胞瘤细胞的增殖,表明其治疗潜力.
结论:
- 核糖体生物发生抑制是神经母细胞瘤的一个有前途的治疗策略.
- 支持扩大治疗目标,包括像FBL这样的rRNA成熟因子.
- 向核糖体生物生成为神经母细胞瘤治疗提供了一种新的方法.
相关概念视频
The 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
Ribosome Profiling
3.4K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.4K
Translation
14.2K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
14.2K
Leaky Scanning
5.0K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.0K
The 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
Improving Translational Accuracy
8.5K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
8.5K


