在肝细胞癌中维持昼夜节律
Yanyan Yang1, Ashraf N Abdo1, Hiroaki Kawara1
1Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
The Journal of biological chemistry
|September 15, 2023
概括
与健康细胞相比,癌性肝细胞表现出不同的日常基因表达模式,这为基于时间的癌症药物治疗提供了潜力. 这项研究分析了小鼠肝癌模型中的昼夜节律.
科学领域:
- 时间生物学 时间生物学
- 癌症研究 癌症研究
- 基因组学就是基因组学.
背景情况:
- 循环节律由分子钟控制,调节组织中的基因表达.
- 新生体组织经常表现出改变的昼夜功能.
- 之前的研究表明瘤中异常的昼夜控制.
研究的目的:
- 在肝癌的小鼠模型中研究全基因组的昼夜节律性.
- 为了比较健康肝脏与癌症组织中的节奏基因表达.
- 探索依赖时间的癌症治疗的潜力.
主要方法:
- 一个小鼠肝癌模型是使用diethylnitrosamine建立的.
- 携带瘤和对照小鼠在24小时内每隔2小时注射一次西斯丁.
- 在注射后2小时使用切除修复序列 (XR-Seq) 分析基因表达.
主要成果:
- 核心时钟基因在健康的肝脏和瘤中都表现出节奏表达,瘤显示出更高的幅度和阶段进步.
- 尽管有相似数量的节律基因,但正常和癌症肝细胞之间只有~10%的重叠.
- 只有在瘤中节奏表达的基因在白天达到峰值,与健康的肝脏基因在黎明前/黄昏前达到峰值不同.
结论:
- 肝癌显著改变了时钟控制基因的昼夜表达.
- 瘤中独特的时间基因表达模式为优化抗癌药物递送提供了潜在的窗口.
- 根据基因表达特征的差异,西斯普拉丁治疗的时间可能会影响治疗疗效.
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