功能获取突变p53调节长非编码RNA LINC00643以调节质母细胞瘤中的HIF1α
Ying Zhang1, Fang Yuan1, Myron Keith Gibert1
1Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
通过抑制LINC00643长非编码RNA,p53 (GOF-MUT-p53) 瘤基因的功能获取突变驱动质母细胞瘤. 这种抑制会破坏HIF1α通路,促进瘤生长并影响患者的生存.
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 是一个
背景情况:
- 在p53中获得功能的突变 (GOF-MUT-p53) 通过改变基因转录来作为瘤基因起作用.
- 质母细胞瘤 (GBM) 是一种具有复杂分子基础的高度攻击性的脑瘤.
研究的目的:
- 在GBM中确定GOF-MUT-p53的全基因组转录标.
- 阐明长非编码RNALINC00643在GBM病原发生中的作用及其由GOF-MUT-p53.3调节的作用.
主要方法:
- 对GOF-MUT-p53转录标进行全基因组查.
- 在质瘤组织中LINC00643表达的定量分析.
- 功能性测试评估LINC00643对GBM细胞行为的影响.
- 通过RNA净化分离染色体,然后进行测序 (ChIRP-seq) 来识别相互作用体.
- 低氧研究是为了研究路径调节.
主要成果:
- 一个GOF-MUT-p53目标的子集包括长非编码RNA (lncRNAs),特别是LINC00643.
- 在GBM和低度结质瘤中,LINC00643的下调,与患者存活率较差相关.
- LINC00643抑制了GBM细胞的增殖,迁移,入侵,干细胞和瘤的生长.
- LINC00643与HIF1α相互作用,抑制其表达,并在低氧下下游准.
- GOF-MUT-p53 knockdown可以调节LINC00643并降低HIF1α水平.
结论:
- 在GBM中,GOF-MUT-p53广泛调节lncRNA.
- GOF-MUT-p53通过抑制LINC00643驱动GBM,从而导致HIF1α通路的失调.
- 在GBM中,LINC00643充当瘤抑制剂,提供潜在的治疗标.
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