Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, Jiangsu 210009, China; Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, Jiangsu 210009, China.
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, Jiangsu 210009, China.
Ecotoxicol Environ Saf. 2019 Mar;169:863-873. doi: 10.1016/j.ecoenv.2018.11.114. Epub 2018 Nov 29.
PM2.5 has implications in cardiovascular adverse events, but the underlying mechanisms are still obscure. The aim of this study is to evaluate miRNA expression in endothelial cells in response to two realistic doses of PM2.5 and to identify the possible gene targets of deregulated miRNAs through microarray profiling and computational technology. As a result, there are 18 differentially expressed miRNAs between 2.5 μg/cm group and the control, of which 11 miRNAs are up-regulated and 7 miRNAs are down-regulated. Relative to the control group, 40 miRNAs are significantly changed in 10 μg/cm group with 21 miRNAs being upregulated and 19 miRNAs being downregulated. Interestingly, when two PM2.5-treated groups respectively compared with the control, the expressed trends of 12 miRNAs in 2.5 μg/cm group are the same as those in 10 μg/cm group, with 8 being upregulated and 4 miRNAs being simultaneously downregulated. Gene ontology (GO) analysis shows that the crucial functional categories of miRNA-targeted genes incorporate transcription-related process and intracellular signal transduction. Pathway analysis reveals that endocytosis, FoxO signaling pathway and PI3K-Akt signaling pathway are involved in the PM2.5-caused cardiotoxicity. Further confirmation by RT-qPCR indicates that PM2.5 could induce the down-regulation of hsa-miR-128-3p, hsa-miR-96-5p, hsa-miR-28-5p, hsa-miR-4478 and hsa-miR-6808-5p, which are in accordance with the results of array data. With the comprehensive analysis of mRNAs and miRNAs, a great number of pairs have been identified, suggesting abnormally expressed miRNAs have functions in the cardiotoxicity of PM2.5, and the function may be achieved through the post-transcriptional regulation of certain genes on the related pathways.
PM2.5 对心血管不良事件有影响，但潜在机制尚不清楚。本研究旨在评估内皮细胞对两种实际剂量 PM2.5 的反应中 miRNA 的表达，并通过微阵列分析和计算技术鉴定失调 miRNA 的可能基因靶标。结果显示，2.5μg/cm 组与对照组之间有 18 个差异表达 miRNA，其中 11 个 miRNA 上调，7 个 miRNA 下调。与对照组相比，10μg/cm 组有 40 个 miRNA 显著改变，其中 21 个上调，19 个下调。有趣的是，当两个 PM2.5 处理组分别与对照组比较时，2.5μg/cm 组中 12 个 miRNA 的表达趋势与 10μg/cm 组相同，其中 8 个上调，4 个 miRNA 同时下调。GO 分析表明，miRNA 靶基因的关键功能类别包括转录相关过程和细胞内信号转导。通路分析显示，内吞作用、FoxO 信号通路和 PI3K-Akt 信号通路参与 PM2.5 引起的心脏毒性。进一步的 RT-qPCR 验证表明，PM2.5 可诱导 hsa-miR-128-3p、hsa-miR-96-5p、hsa-miR-28-5p、hsa-miR-4478 和 hsa-miR-6808-5p 的下调，与芯片数据结果一致。通过对 mRNAs 和 miRNAs 的综合分析，鉴定出大量的配对，提示异常表达的 miRNAs 在 PM2.5 的心脏毒性中具有功能，该功能可能通过相关通路中某些基因的转录后调控来实现。
