循环RAPGEF5通过调解HOXC6稳定性来促进LUAD
Li Jia1, Lijuan Zhang1, Dongjie Wang1
1Department of Respiratory Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
概括
循环RNAcircRAPGEF5通过稳定HOXC6mRNA和激活HOXB2.2促进肺腺癌 (LUAD) 的进展. 准circRAPGEF5和HOXC6为LUAD治疗提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 肺腺癌 (LUAD) 是癌症死亡的主要原因,通常在晚期诊断时预后不佳.
- 驱动LUAD进展的特定分子机制,特别是涉及HOXC6,仍然不完全理解.
研究的目的:
- 阐明HOXC6在肺腺癌 (LUAD) 进展中的作用和分子机制.
- 调查LUAD中涉及circRAPGEF5,HOXC6和HOXB2的监管网络.
主要方法:
- 量化逆转录PCR (RT-qPCR),免疫组织化学 (IHC),西斑,免疫光 (IF),CCK-8,划痕和Transwell试验被用于评估基因/蛋白质表达和细胞行为.
- 使用染色体免疫沉降 (ChIP),RNA免疫沉降 (RIP) 和双化酶记者测试来探索分子相互作用.
- 在体内异种移植和转移性小鼠模型,以及光在位杂交 (FISH),被用来评估瘤生长和转移.
主要成果:
- 抑制circRAPGEF5显著抑制了LUAD细胞的增殖,迁移,入侵,瘤生长和体内转移.
- circRAPGEF5通过与HNRNPC相互作用来增强HOXC6mRNA的稳定性,从而导致HOXC6表达的增加.
- HOXC6通过转录激活HOXB2,而HOXC6的过度表达可以逆转circRAPGEF5敲击的抑制作用.
结论:
- circRAPGEF5通过通过HNRNPC稳定HOXC6mRNA并随后激活HOXB2转录来促进LUAD进展和转移.
- 针对circRAPGEF5/HOXC6/HOXB2轴为肺腺癌提供了潜在的治疗策略.
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