Circulating miRNAs as molecular markers of occupational grain dust exposure

Abstract

Dust from grain and feed production may cause adverse health effects in exposed workers. In this study we explored circulating miRNAs as potential biomarkers of occupational grain dust exposure. Twenty-two serum miRNAs were analyzed in 44 grain dust exposed workers and 22 controls. Exposed workers had significantly upregulated miR-18a-5p, miR-124-3p and miR-574-3p, and downregulated miR-19b-3p and miR-146a-5p, compared to controls. Putative target genes for the differentially expressed miRNAs were involved in a range of Kyoto Encyclopedia of Genes and Genomes signaling pathways, and 'Pathways in cancer' and 'Wnt signaling pathway' were common for all the five miRNAs. MiRNA-diseases association analysis showed a link between the five identified miRNAs and several lung diseases terms. A positive correlation between miR-124-3p, miR-18a-5p, and miR-574-3p and IL-6 protein level was shown, while miR-19b-3p was inversely correlated with CC-16 and sCD40L protein levels. Receiver-operating characteristic analysis of the five miRNA showed that three miRNAs (miR-574-3p, miR-124-3p and miR-18a-5p) could distinguish the grain dust exposed group from the control group, with miR-574-3p as the strongest predictor of grain dust exposure. In conclusion, this study identified five signature miRNAs as potential novel biomarkers of grain dust exposure that may have potential as early disease markers. Workers at grain elevators and animal feed mills are exposed to grain dust containing a complex mixture of inorganic and organic particles from soil, plants, insects and microorganisms, and includes components such as endotoxins, β-1,3-glucans and mycotoxins 1,2. The individual dust components have the ability to induce inflammatory and allergic responses, and symptoms from the airways are frequently observed among grain handlers 3-8. Endotoxin has been proposed as a target for measurements of occupational health hazard of grain dust 9 , but depending on the grain dust composition, other components in the dust may be stronger associated with health effects. Diverging exposure-response relationships have indeed been observed between studies 2,3,10-12. Although exact mechanisms are not completely elucidated, the pathological response to grain dust exposure may include activation of inflammatory and allergic pathways. miRNAs are small non-coding RNA molecules that regulate gene expression by binding to specific mRNAs, which leads to either degradation of the mRNA or inhibition of translation, thus suppressing gene activity 13. Several studies have suggested that the toxicity of environmental chemicals are mediated by miRNAs 14 , and particular miRNA profiles have been associated with different diseases, such as asthma, COPD and cancer 15. Little is known about the miRNA induction following grain dust exposure. However, it is shown that miR-146a are induced by LPS and other proinflammatory mediators such as TNFα, IL-1β and CD40L 16. Epigenetic studies in mice models suggests a role for increased miR-146a in allergic rhinitis 17. Reduced exp...

Changes in miRNA expression in the lungs of pigs supplemented with different levels and forms of vitamin D

“…On the other hand, we can reach different conclusions by analyzing the change in miR-574 expression (upregulation). The results of research conducted on a group of healthy individuals exposed to feed dust suggest that increased expression of miR-574 is a good predictor of such exposure [ 35 ]. Moreover, oncology studies also point to negative effects associated with increased miR-574 expression.…”

The effects of maternal cigarette smoking on cadmium and lead levels, miRNA expression and biochemical parameters across the feto-placental unit

“…The authors found that a high concentration of cotinine in urine (as a measure of maternal smoking) was associated with miR-223 in maternal and cord blood. Although there is a lack of literature data on the effect of smoking on the expression of circulating miRNAs, the existing evidence have so far shown that air pollutants [ 57 ], working conditions [ 58 , 59 ] and metal exposure [ 60 ] might affect the regulation of circulating miRNA.…”

The airborne mycobiome and associations with mycotoxins and inflammatory markers in the Norwegian grain industry

“…Other response markers of microbial exposure, such as increases serum amyloid A and C-reactive protein has been shown to be affected by the species composition in green houses 26 . We have previously shown differences in inflammatory markers and circulating miRNAs in blood of exposed workers compared to unexposed controls without finding any association with exposure measurements 27 , 28 . However, the complete assemblage of fungal species in the Norwegian grain elevators and animal feed mills has not been properly evaluated.…”