基于数据驱动的基于斑马鱼作用的TCS在AOP框架中的关键circRNA事件的分析
Zejun Wang1, Xiaowen Han1, Xincong Su1
1National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.
Ecotoxicology and environmental safety
|June 5, 2024
概括
特里克洛桑 (TCS) 暴露通过circRNA和microRNA (miRNA) 相互作用破坏基因表达,导致毒性. 这项研究建立了一个不良结果途径 (AOP) 框架,以解释斑马鱼中TCS毒性机制.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 特里克洛桑 (TCS) 是个人护理产品中常见的抗生素,具有毒性,包括神经毒性和心脏毒性.
- TCS毒性机制与microRNA (miRNA) 失调有关,但上游调节途径尚不清楚.
研究的目的:
- 用斑马鱼的circRNA表达数据研究TCS诱导的miRNA失调的上游机制.
- 构建一个全面的不良结果途径 (AOP) 框架,阐明TCS毒性.
主要方法:
- 在暴露于TCS的斑马鱼幼虫中对circRNA表达的层次分析.
- 对circRNA宿主基因的基因本体学 (GO) 和KEGG通路分析.
- 竞争性内源RNA (ceRNA) 网络的构建和优化.
- 通过circRNA48敲除和毒性终点评估验证AOP框架.
主要成果:
- 确定了29个关键的circRNA事件来调节miRNA的表达.
- 建立了一个详细描述circRNA-miRNA相互作用的ceRNA网络.
- 开发了一个多层次的AOP框架,包括circRNA,miRNA,mRNA,途径和毒性.
- 通过circRNA48敲击证明了AOP框架的有效性,显示了对miRNA水平的影响以及神经毒性和心脏毒性等不良结果.
结论:
- 这项研究确定了TCS毒性中miRNA失调的上游关键circRNA事件.
- 开发的AOP框架提供了对斑马鱼TCS毒性机制的系统理解.
- 这些发现为TCS暴露的危险评估和控制提供了理论基础.
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