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和紫外线的同时暴露会产生独特的基因表达特征,识别关键的共同致癌机制
Rachel M Speer1, Hui Yu2, Xixi Zhou1
1Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
与紫外线辐射 (UVR) 结合的暴露会导致协同的基因表达变化,与单个暴露不同. 这些基因表达的变化可能会推动UVR诱导的皮肤癌的共同致癌.
科学领域:
- 环境毒理学环境毒理学
- 分子致癌症的产生.
- 基因组学就是基因组学.
背景情况:
- 基因表达的变化是致病的基础,包括癌症的发展.
- 是一种已知的共同致癌物质,可增强紫外线诱导的皮肤癌,但其在这种情况下对基因表达的影响尚不清楚.
- 了解共同暴露的分子机制对于评估联合环境风险至关重要.
研究的目的:
- 为了研究由和紫外线照射相结合而产生的独特基因表达特征.
- 确定特定的细胞通路和机制,涉及增强紫外线致癌.
- 为了区分基因表达应对联合暴露和单个或紫外线暴露的反应.
主要方法:
- 用RNA测序 (RNA-seq) 分析来分析基因表达.
- 对单独的,单独的紫外线和组合的-紫外线暴露进行了差异基因表达分析.
- 用基因本体学 (GO) 分析来解释差异表达基因 (DEG) 的功能意义.
主要成果:
- 与单个暴露相比,和紫外线照射的联合暴露导致了DEG数量的协同增长.
- 大多数来自联合暴露的DEG是独一无二的,表明了明显的分子反应.
- 和-UVR联合暴露主要导致全球基因下调.
- GO分析显示,联合暴露向细胞过程,包括染色体不稳定性,细胞周期,细胞转化,信号和表观遗传修饰 (基因组修饰).
结论:
- 和紫外线的联合暴露会诱导一种独特和协同的基因表达特征.
- 这些独特的基因表达变化,特别是影响染色体稳定性和细胞转换的变化,可能是对UVR诱导的皮肤癌的共同致癌作用的关键驱动因素.
- 这些发现提供了对增强紫外线致癌的分子机制的关键见解.
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