通过调解CRaf/MEK/ERK通路,RUVBL1加速了舌头状细胞癌的发生
Xin-Yu Zhang1, Yang Liu2, Qiong Rong1
1The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province 650032, China.
iScience
|March 25, 2024
概括
通过激活RAF/MEK/ERK通路,RUVBL1促进了舌状细胞癌 (TSCC) 的进展. 较低的RUVBL1表达与更好的患者存活率相关,这表明它是治疗目标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 在各种瘤中,RAF/MEK/ERK信号通路经常被激活.
- 了解RAF结合蛋白 (RUVBL1) 在舌状细胞癌 (TSCC) 中的作用至关重要.
研究的目的:
- 为了研究RUVBL1在TSCC中的功能.
- 阐明RUVBL1影响TSCC进展的分子机制.
- 在TSCC中探索RUVBL1作为潜在的治疗点.
主要方法:
- 对TCGA-口腔状细胞癌,GSE13601和GSE34105数据集的生物信息分析,以识别差异表达的mRNA.
- 使用CAL-27和SCC-4细胞系进行体外研究,以评估RUVBL1过度表达和淘汰对细胞活力,迁移,入侵,球体形成,血管生成和耐药性的影响.
- 在体内研究评估RUVBL1对瘤生长的影响.
- 西部斑点分析以检查CRAF和下游MEK/ERK路径组件的酸化状态.
主要成果:
- 确定了672个共享的差异表达mRNA,主要调节转移和血管生成.
- 低RUVBL1表达与TSCC患者的整体存活率改善有关.
- 过度表达RUVBL1增强了TSCC细胞活力,迁移,入侵,球体形成,血管生成和抗化学疗法 (cisplatin和5-fluorouracil) 的抵抗力.
- 相反,对RUVBL1的抑制产生了相反的效果.
- 在体内,RUVBL1的过度表达促进了瘤的生长.
- RUVBL1减少了CRAF Ser259酸化,导致MEK/ERK通路的激活.
结论:
- RUVBL1对TSCC的恶性生物行为有显著的贡献.
- RUVBL1激活了CRAF/MEK/ERK通路,促进了TSCC的进展.
- RUVBL1代表了TSCC治疗的潜在分子标.
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