Comprehensive understanding of PM_2.5 on gene and microRNA expression patterns in zebrafish (Danio rerio) model.

PM_2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM_2.5. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM_2.5 is missing. The objective of this study was to evaluate the toxicity of PM_2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM_2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process. Pathway and Signal-net analysis showed that the critical pathway involved in the response to exposure to PM_2.5 was the metabolism of xenobiotics by cytochrome P450. Results from verification experiments also demonstrated that the key genes with degree higher than 10 induced by PM_2.5 were related to metabolism of xenobiotics by cytochrome P450, including cyp3a65, mgst2, gstp1, gsto2, gsto1, cyp1a, ehx1, gstal and aldh3b1. The differential expression of 8 microRNAs corresponding to those in the human genome, revealed that PM_2.5 could up-regulate let-7b, miR-153b-3p, miR-122, miR-24 and down-regulate let-7i, miR-19a-3p, miR-19b-3p and miR-7a, which suggested PM_2.5 had multiple means through which it induced toxicity in living organisms, such as suppression of adaptive immune responses, autophagy, deregulation of metabolism, impaired vasorelaxation, progression of cancers, as well as hypertension, atherosclerosis and myocardial infarction. Copyright © 2017 Elsevier B.V. All rights reserved.

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