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在肝细胞癌细胞中,sorafenib相关的翻译重编程

Laura Contreras^1,2, Alfonso Rodríguez-Gil^1,3, Jordi Muntané^1,3,4

¹Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.

|March 21, 2025

概括

索拉芬尼 (Sfb) 抑制了肝癌细胞的全球蛋白质合成,但选择性地调高了特定基因的翻译. 这种适应性翻译重编程为新的组合疗法提供了洞察力.

科学领域:

分子生物学分子生物学
生物化学生化学
在瘤学瘤学.

背景情况:

索拉芬尼 (Sorafenib,Sfb) 是一种用于晚期肝细胞癌 (HCC) 的多酶抑制剂,适度改善了生存率.
在癌细胞中,Sfb抑制了蛋白质合成的启动.
在HCC中Sfb对mRNA翻译的全球影响仍然未被探索.

研究的目的:

为了研究在HCC细胞中Sfb治疗后mRNA翻译的全基因组变化.
为了确定受Sfb诱导的翻译重编程影响的特定基因和通路.
了解Sfb对翻译的影响的机制及其对治疗的影响.

主要方法:

在Sfb处理的HCC细胞中进行全基因组多体形分析.
翻译效率与mRNA cis作用元素和蛋白质因子 (例如,DAP5,ARE结合蛋白) 的相关性分析.
分析受Sfb诱导的转化变化影响的生物过程.

主要成果:

全球翻译被Sfb抑制,但基因的一个子集显示持续或诱导的翻译.
翻译控制与mRNA cis-acting元素和特定的RNA结合蛋白有关.
Sfb治疗降低了线粒体代谢和原蛋白合成基因的翻译.
Sfb对参与细胞适应和应激反应的途径的翻译进行上调.

结论:

索拉芬尼 (Sfb) 在肝细胞癌 (HCC) 细胞中诱导了适应性翻译重编程.
这种重编程涉及选择性基因翻译调制,受mRNA元素和RNA结合蛋白的影响.
研究结果为Sfb的作用机制提供了洞察力,并表明了新型组合疗法的潜力.

关键词:

肝细胞癌是肝细胞癌.索拉费尼布 (Sorafenib) 是一种 m6A甲基化的情况.多组体概况分析 (polysome profiling) 是一种多组体概况分析方法.翻译翻译翻译翻译翻译翻译

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