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/cm2 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/cm2 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/cm2 group are the same as those in 10 μg/cm2 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.
Keywords: Bioinformatics; Cardiovascular toxicity; Fine particulate matter; MicroRNA; Microarray; PI3K-Akt signaling pathway.
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