Integrative Analysis of miRNA and Inflammatory Gene Expression After Acute Particulate Matter Exposure

Exposure, Epidemiology and Risk Program, Department of Environmental Health, Laboratory of Environmental Epigenetics, Harvard School of Public Health, 665 Huntington Avenue, KRESGE Building 1, Boston, MA 02115, USA. Phone: (617) 432-0666. Fax: (617) 384-8859.
Toxicological Sciences (Impact Factor: 3.85). 01/2013; 132(2). DOI: 10.1093/toxsci/kft013
Source: PubMed


MicroRNAs are environmentally-sensitive inhibitors of gene expression that may mediate the effects of metal-rich particulate matter (PM) and toxic metals on human individuals. Previous environmental miRNA studies have investigated a limited number of candidate miRNAs and have not yet evaluated functional effects on gene expression. In this study we want to identify PM-sensitive miRNAs using microarray profiling on matched baseline and post-exposure RNA from foundry workers with well-characterized exposure to metal-rich PM; and to characterize miRNA relations with expression of candidate inflammatory genes.We applied microarray analysis of 847 human miRNAs and Real-Time PCR analysis of 18 candidate inflammatory genes on matched blood samples collected from foundry workers at baseline and after three days of work (post-exposure). We identified differentially-expressed miRNAs (Fold Change [FC]>2 and p<0.05) and correlated their expression with the inflammatory associated genes. We performed in-silico network analysis in MetaCore v6.9 to characterize the biological pathways connecting miRNA-mRNA pairs.Microarray analysis identified four miRNAs that were differentially-expressed in post-exposure compared to baseline samples, including miR-421 (FC=2.81, p-value<0.001), miR146a (FC=2.62, p-value=0.007), miR-29a (FC=2.91, p-value<0.001), and let-7g (FC=2.73, p-value=0.019). Using FDR adjustment for multiple comparisons, we found 11 miRNA-mRNA correlated pairs involving the four differentially-expressed miRNAs and candidate inflammatory genes. In-silico network analysis with MetaCore database identified biological interactions for all the 11 miRNA-mRNA pairs, which ranged from direct mRNA targeting to complex interactions with multiple intermediates.Acute PM exposure may affect gene-regulation through PM-responsive miRNAs that directly or indirectly control inflammatory gene expression.

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    • "The investigation of short term effects of metal-rich PM on miRNA expression in pre-and post-exposure samples from steel production plant workers, highlighted 4 up-regulated miRNA in post-exposure compared with baseline samples (Motta et al., 2013). Concomitant mRNA analysis provided evidence on the impact of acute PM exposure on gene regulation through novel PMresponsive miRNA that may directly or indirectly control inflammatory gene expression (Motta et al., 2013). Subsequently, Fossati and collaborators analyzed the association between PM exposure and miRNA deregulation in elderly men; they found a down-regulation in candidate miRNA involved in processes related to PM exposure, including inflammation, endothelial dysfunction, and coagulation (Fossati et al., 2014). "
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