异常基因突变的分子特征和由肝细胞癌细胞中子烯诱导的表达特征
Xinyi Cao1, Ying Zhu2, Shujun Cheng1
1School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Toxics
|July 26, 2024
概括
长期低剂量暴露于致癌物甲 (BaP),促进人类肝细胞癌 (HCC) 细胞转移. BaP改变基因表达,外体载荷和突变,可能重塑瘤微环境.
科学领域:
- 在瘤学瘤学.
- 环境健康 环境健康
- 分子生物学分子生物学
背景情况:
- 甲 (BaP) 是一种常见的食品和环境致癌物.
- 慢性低剂量BaP暴露与人类肝细胞癌 (HCC) 细胞的迁移和入侵增加有关.
- 驱动BaP诱导的HCC转移的精确分子机制尚未完全理解.
研究的目的:
- 在人类肝细胞癌 (HCC) 细胞中研究慢性低剂量甲 (BaP) 暴露引起的分子变化.
- 为了阐明基因表达变化的作用,外体RNA载荷和BaP驱动的HCC转移中的遗传变异.
- 探索这些改变对瘤微环境的潜在影响.
主要方法:
- 为全面分析建立了暴露于BaP的HCC细胞模型.
- 利用转录组和全基因组测序来分析基因表达,外体RNA和遗传变异.
- 构建的外体环RNA-miRNA-mRNA相互作用网络.
主要成果:
- 转录组分析揭示了转移相关基因和途径的显著失调,包括类固醇脂代谢和细胞迁移.
- 对BaP的暴露丰富了PI3K-AKT,mTOR和NF-κB信号通路,并破坏了参与细胞分泌过程的基因.
- 全基因组测序确定了HCC细胞中BaP诱导的基因突变和基因组不稳定性,并观察到改变的外体RNA配置文件.
结论:
- 长时间低剂量的BaP暴露会诱导HCC细胞的复杂分子变化,影响基因突变,表达和外体含量.
- 这些变化,特别是在外体内,可能有助于瘤微环境的重塑,并促进HCC转移.
- 这些发现为BaP诱导的HCC转移和BaP毒性的分子机制提供了新的见解.
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