Differential Circulating miRNA Responses to PM Exposure in Healthy and Diabetes Mellitus Patients: Implications for Lung Cancer Susceptibility

TL;DR

The study finds that diabetes mellitus alters how microRNA levels respond to air pollution, suggesting potential biomarkers for lung cancer risk.

Contribution

The study identifies PM-responsive circulating miRNAs and shows how diabetes mellitus modifies these responses.

Findings

Four miRNAs (miR-542-3p, miR-29a-3p, novelmiR-203, and novelmiR-754) showed differential expression in response to PM exposure.

DM patients exhibited altered baseline miRNA levels and different seasonal changes compared to non-DM individuals.

miR-542-3p was significantly different between lung cancer patients and healthy controls.

Abstract

Seasonal biomass-burning haze in Northern Thailand produces sharp fluctuations in ambient fine particulate matter (PM), posing heightened health risks, particularly for individuals with diabetes mellitus (DM). To identify PM-responsive biomarkers and assess whether metabolic status modifies these responses, we first performed small RNA sequencing in a discovery cohort using plasma samples collected during low- and high-PM periods. Thirteen circulating microRNAs (miRNAs) were differentially expressed, including reduced miR-542-3p and elevated miR-29a-3p, novelmiR-203, and novelmiR-754, with predicted targets enriched in immune and endoplasmic-reticulum stress pathways. These four miRNAs were quantified by RT-qPCR in a longitudinal cohort of adults with (n = 28) and without DM (n = 29) sampled at three PM-defined timepoints across one full haze cycle. In non-DM individuals, miR-542-3p decreased at peak exposure while miR-29a-3p and novelmiR-203 increased, with values returning toward baseline at re-exposure. DM participants showed altered baseline levels and attenuated or reversed seasonal changes. Plasma IL-8 rose markedly at peak PM in both groups, mirroring exosome concentration increases measured by NTA, indicating a transient systemic inflammatory response. In an independent clinical cohort, only miR-542-3p differed significantly between lung-cancer patients and healthy controls. These findings indicate that PM exposure reconfigures circulating miRNA, exosomal, and cytokine profiles, and that DM modifies these responses, highlighting miR-542-3p and miR-29a-3p as environmentally responsive and disease-relevant biomarker candidates.

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