Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that act as post-transcriptional regulators by silencing messenger RNAs. Because miRNAs do not rapidly degrade, they have the potential to serve as sensitive, predictive, and robust non-invasive biomarkers in bodily fluids. While urinary miRNAs have been used as clinical biomarkers of disease, their roles as potential biomarkers of occupational and environmental exposures has yet to be elucidated. Our study investigated miRNA profiles from archived urinary samples and identified miRNAs associated with occupational exposure to pesticides in farmworkers. Urinary samples were collected from a nested cohort of 27 farmworkers and non-farmworkers (16FW/11 NFW) during two agricultural seasons. MiRNAs were isolated and profiled using PCR arrays. Comparisons were made between occupational and seasonal exposure. Principal components and hierarchical clustering analyses of the ten most frequently expressed miRNAs among groups indicate significant differences in miRNA profiles between farmworker and non-farmworker adults. A seasonal difference in miRNA profiles was observed in farmworkers. Six miRNAs were observed to be associated with farmworker occupation during the post-harvest season. A positive dose-response relationship was observed between five of the farmworker-associated miRNAs and organophosphate pesticide metabolites. Four of the miRNAs associated with farmworker occupation have been associated with target genes involved in neurological functions including neurotransmitter activity and receptor binding. One of the miRNAs associated with farmworker occupation has been associated with acetylcholine binding, acetylcholinesterase activity, and cholinesterase activity which are hallmark pathways affected by organophosphate pesticide exposure. Our findings suggest that miRNA profiles may be novel epigenetic biomarkers of occupational pesticide exposure and early biological response.