通过综合生物信息学和实验验证验,PRC1作为威尔姆斯瘤的独立不良预后因素
Yanping Wang1, Hongjie Gao2, Xuetian Li1
1Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, China.
Scientific reports
|April 17, 2025
概括
在威尔姆斯瘤 (WT) 中,细胞动力学1调节蛋白 (PRC1) 过度表达,导致转移和生存率低下. 向PRC1可能为这种儿科癌提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 威尔姆斯瘤 (WT) 是一种异质的儿科癌,结果各不相同.
- 表皮-介质细胞过渡 (EMT) 促进癌症的进展,迁移和入侵.
- 细胞动力学蛋白调节剂1 (PRC1) 与各种癌症的预后不佳有关.
研究的目的:
- 研究PRC1作为WT的预后因素的作用.
- 阐明PRC1在WT进展中的功能背后的机制.
- 探索PRC1作为潜在的治疗标和WT的生物标志物.
主要方法:
- 大量和单细胞RNA-seq数据的生物信息分析 (TARGET,GSE200256).
- 功能丰富分析 (GO,KEGG,GSEA) 和免疫分析.
- 对拷贝数变异 (CNVs) 和微RNA失调的基因组分析.
- 在体外实验中,在WT细胞中进行了PRC1倒置的实验 (WIT-49).
主要成果:
- 在WT中,PRC1显著上调,并与整体存活率差相关.
- PRC1与致癌途径 (Wnt/β-catenin,PI3K/AKT/mTOR,Hedgehog) 的激活以及免疫细胞活动 (NK细胞) 的降低相关.
- PRC1表达在形WT (AWT) 中较高,并且与EMT和转移有关.
- PRC1的淘汰破坏了WT细胞的迁移,入侵,EMT和糖解.
结论:
- PRC1是WT进展,转移和免疫逃避的关键驱动因素.
- PRC1的过度表达是由CNV和下调的microRNA驱动的.
- PRC1代表了一个有前途的预后生物标志物和威尔姆斯瘤的治疗标.
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