计算分析揭示了与夜班工人乳腺癌发展相关的放松调节的时钟基因
Silvia Vivarelli1, Giovanna Spatari1, Chiara Costa2
1Department of Biomedical and Dental Sciences, Morphological and Functional Imaging, Section of Occupational Medicine, University of Messina, 78712 Messina, Italy.
夜班工作 (NSW) 通过破坏昼夜节律,增加了乳腺癌 (BC) 的风险. 时钟基因和microRNAs表现出改变的表达,表明它们作为夜班工人BC易感性生物标志物的潜力.
科学领域:
- 在瘤学瘤学.
- 时间生物学 时间生物学
- 分子生物学分子生物学
背景情况:
- 乳腺癌 (BC) 是全球女性癌症死亡的主要原因.
- 夜班工作 (NSW) 与BC风险增加有关,可能是由于昼夜节律扰乱.
- 将新南威尔士州与BC风险联系起来的分子机制尚不清楚.
研究的目的:
- 调查长期暴露在新南威尔士州的妇女中的时钟基因作为BC的潜在生物标志物.
- 确定分子机制,包括由miRNAs影响的转录后调节,受新南威尔士的影响.
主要方法:
- 从护士健康研究中对乳腺癌和正常组织的时钟基因表达的分析.
- 使用额外的基因表达数据集和单细胞测序数据进行验证.
- 识别小RNA调节器的时钟基因.
主要成果:
- 与正常组织相比,在BC组织中观察到钟基因表达的显著变化.
- 一些特定的时钟基因 (BHLHE40,CIART,CLOCK,PDPK1,TIMELESS) 过度表达,而其他 (HLF,NFIL3,NPAS3,PER1,PER3,SIM1,TEF) 则表达不足.
- 对PER1/TEF的下调和对CLOCK的上调与增加的BC风险相关;26个miRNA被确定为潜在的新南威尔士影响的调节者.
结论:
- 一组时钟基因和昼夜miRNA被提议作为夜班工作者BC易感性生物标志物.
- 这些发现支持对这一群体的风险分层和早期BC检测策略的潜在应用.
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