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DIFFERENTIAL EXPRESSION OF MICRORNAS IN SUBJECTS EXPOSED TO METAL RICH PARTICULATE MATTER

2011; National Institute of Environmental Health Sciences; Volume: 2011; Issue: 1 Linguagem: Inglês

10.1289/isee.2011.00616

2169-2181

Laura Angelici, Valeria Motta, Francesco Nordio, Fabio Frascati, Valentina Tinaglia, Valentina Bollati, Pier Alberto Bertazzi, Cristina Battaglia, Andrea Baccarelli,

Energy and Environment Impacts

Background and Aims: Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate the expression of broad gene networks at the posttranscriptional level. We evaluated the potential effects of exposure to PM and PM metal components on microRNAs expression in 10 workers at an electric-furnace steel plant in Brescia, Italy. Methods: We measured expression in blood leukocyte RNA on the first day of a workweek (baseline, after two days off work) and after 3 days of work (postexposure). All subjects in the study were no smokers with a means age of 46y and a characterized exposure to metal rich PM (about 3 times greater than environmental levels in the same area). Gene expression was profiled at baseline (n=10) and postexposure (n=10) using an Affymetrix GeneChip miRNA Array. Differential expression of miRNAs was determined with Limma (R-based Bioconductor package), which employs an empirical Bayes approach to calculate a moderated t-statistic. miRNAs with p < 0.05 and the absolute value of FC >2 were considered as differential miRNAs (DEMs). Predicted miRNA targets were determined using the miRanda algorithm, DEMs were subjected to pathway exploration using the Ingenuity Pathway Analysis (IPA) software. Results: Four miRNAs – hsa-miR-421, hsa-miR-29, hsa-miR-146, hsa-let-7g – were found to be up-regulated. Bioinformatics analysis on these selected miRNAs showed as top ranked network RNA Post-Transcriptional Modification and Cell Morphology whereas the main diseases and disorders involved were Genetic Disorder, Cardiovascular Disease and Neurological Disease. Conclusions: Changes in miRNAs expression may represent a novel mechanism mediating responses to PM and its metal components.