The potential role of plasma miR-4301 in PM exposure-associated lung function reduction.

The effect of PM exposure on lung function reduction has been well-documented, but the underlying mechanism remains unclear. MiR-4301 may be involved in regulating pathways related to lung injury/repairment, and this study aimed to explore the potential role of miR-4301 in PM exposure-associated lung function reduction. A total of 167 Wuhan community nonsmokers were included in this study. Lung function was measured and personal PM exposure moving averages were evaluated for each participant. Plasma miRNA was determined by real-time polymerase chain reaction. A generalized linear model was conducted to assess the relationships among personal PM moving average concentrations, lung function, and plasma miRNA. The mediation effect of miRNA on the association of personal PM exposure with lung function reduction was estimated. Finally, we performed pathway enrichment analysis to predict the underlying pathways of miRNA in lung function reduction from PM exposure. We found that each 10 μg/m increase in the 7-day personal PM moving average concentration (Lag0-7) was related to a 46.71 mL, 1.15%, 157.06 mL/s, and 188.13 mL/s reductions in FEV, FEV/FVC, PEF, and MMF, respectively. PM exposure was negatively associated with plasma miR-4301 expression levels in a dose‒response manner. Additionally, each 1% increase in miR-4301 expression level was significantly associated with a 0.36 mL, 0.01%, 1.14 mL/s, and 1.28 mL/s increases in FEV, FEV/FVC, MMF, and PEF, respectively. Mediation analysis further revealed that decreased miR-4301 mediated 15.6% and 16.8% of PM exposure-associated reductions in FEV/FVC and MMF, respectively. Pathway enrichment analyses suggested that the wingless related-integration site (Wnt) signaling pathway might be one of the pathways regulated by miR-4301 in the reduction of lung function from PM exposure. In brief, personal PM exposure was negatively associated with plasma miR-4301 or lung function in a dose‒response manner. Moreover, miR-4301 partially mediated the lung function reduction associated with PM exposure.