Integrated analysis of microRNA and mRNA expression profiles highlights alterations in modulation of the apoptosis-related pathway under nonanal exposure

Abstract

We have shown that aldehydes impact gene expression profiles of bronchial airway associated with pulmonary toxicity. In this study, we aimed to determine whether microRNA (miRNA) plays a role in regulating the airway gene expression response to aldehyde exposure. We analyzed whole genome miRNA and mRNA expression profiles upon nonanal exposure of human alveolar epithelial cells to identify nonanalsensitive miRNAs and to characterize the relationships between miRNAs and the expression of the candidate target genes involved in aldehyde-induced toxicity. Microarray analysis identified six miRNAs that were differentially expressed in nonanal-exposed A549 human alveolar cells. Integrated anti-correlation analyses of miRNA and mRNA expression profiles identified 157 putative target genes. GO analysis of 157 putative target genes demonstrated that the biological category "apoptosis-related pathway" was prominently annotated. Moreover, we detected an increased number of apoptotic cells in the nonanal-exposed group. By integrating the transcriptome and microRNAome, we provide evidence that nonanal can affect apoptosisinduced toxicity signaling. Therefore, this study proves the benefit of an integrated miRNA-mRNA approach for identifying toxicity mechanisms induced by environmental toxicants using an in vitro human model.