Integrative Analysis of mRNA and microRNA Expression of a Human Alveolar Epithelial Cell(A549) Exposed to Water and Organic- Soluble Extract from Particulate Matter (PM)2.5

摘要

MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in tox-icity. In this study, we assessed the effects of particulate matter 2.5 (PM_(2.5)), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM_(2.5)[water (W-PM_(2.5)) and organic (O-PM_(2.5)) soluble extracts] and performed miRNA micro-array analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3-fold in W-PM_(2.5) and O-PM_(2.5), respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W-PM_(2.5) and O-PM_(2.5) exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W-PM_(2.5) target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O-PM_(2.5) target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM_(2.5)-induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model.