Polycyclic aromatic hydrocarbons exposure was associated with microRNA differential expression and neurotransmitter changes: a cross-sectional study in coal miners.

ABSTRACT

Exposure to polycyclic aromatic hydrocarbons (PAHs) may cause neurobehavioral changes. This study aimed to explore the underlying mechanism of PAH neurotoxicity in coal miners. Urinary PAH metabolites, neurotransmitters, and oxidative stress biomarkers of 652 coal miners were examined. Subjects were divided into high and low-exposure groups based on the median of total urinary PAH metabolites. Differentially expressed miRNAs were screened from 5 samples in the low-exposure group (≤ 4.88 µmol/mol Cr) and 5 samples in the high-exposure group (> 4.88 µmol/mol Cr) using microarray technology, followed by bioinformatics analysis of the potential molecular functions of miRNA target genes. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate differentially expressed miRNAs. Restricted cubic splines (RCS) were applied to assess the possible dose-response relationships. Compared to the low PAH exposure group, the high-exposure group had higher levels of 5-hydroxytryptamine (5-HT), epinephrine (E), and acetylcholine (ACh), and lower levels of acetylcholinesterase (AChE). 1-OHP had a dose-response relationship with malondialdehyde (MDA), dopamine (DA), 5-HT, and AChE (P for overall associations < 0.05). There were 19 differentially expressed microRNAs in microarray analysis, significantly enriched in the cell membrane, molecular binding to regulate transcription, and several signaling pathways such as PI3K-Akt. And in the validation stage, miR-885-5p, miR-20a-5p, and let-7i-3p showed differences in the low and high-exposure groups (P < 0.05). Changes in neurotransmitters and microRNA expression levels among the coal miners were associated with PAH exposure. Their biological functions are mainly related to the transcriptional regulation of nervous system diseases or signaling pathways of disorders. These findings provide new insights for future research of PAH neurotoxicity.