生物信息学识别共享的信号通路和核心目标,将佐[a]皮林暴露与HCC进展联系起来
Yong-Le Li1, Rong He1, Meng Tang1
1School of Basic Medicine, Youjiang Medical College for Nationalities, Baise 533000, China.
Toxicology
|April 2, 2025
概括
甲 (BaP) 是一种环境污染物,通过影响线粒体功能和能量代谢,导致肝癌. 像UBA52,NDUFS8和CYP3A4这样的关键基因与BaP诱导的肝损伤和患者生存有关.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 像甲 (BaP) 这样的环境污染物越来越多地与肝癌有关.
- 通过BaP促进肝病的精确分子机制仍然不完全理解.
研究的目的:
- 阐明佐[a]烯在肝癌进展中的作用背后的分子机制.
- 确定与肝细胞癌 (HCC) 相关的BaP暴露影响的关键分子标和途径.
主要方法:
- 使用生物信息数据库 (ChEMBL,SwissTargetPrediction,STITCH,TCGA) 来识别与BaP相关的肝癌目标.
- 进行了基因本体学 (GO) 和基因和基因组 (KEGG) 丰富分析的京都百科全书.
- 构建了蛋白质与蛋白质相互作用 (PPI) 网络,并进行了分子对接研究.
主要成果:
- 确定了169个潜在的目标,富化分析突出了线粒体功能,能量代谢和REDOX反应中的作用.
- 确定了UBA52,NDUFS8,CYP1A2,NDUFS1和CYP3A4作为具有高结合稳定的核心标.
- 在HCC中观察到这些核心基因的显著差异表达,UBA52,NDUFS8和CYP3A4与患者存活率相关.
结论:
- BaP通过涉及线粒体功能和能量代谢的分子途径显著影响肝脏健康.
- 已确定的核心基因 (UBA52,NDUFS8,CYP1A2,NDUFS1,CYP3A4) 在BaP诱导的HCC毒性和患者预后方面至关重要.
- 在HCC内的特定免疫细胞中,UBA52的表达特别高,这表明瘤微环境中的复杂相互作用.
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