Differential Circulating miRNA Responses to PM Exposure in Healthy and Diabetes Mellitus Patients: Implications for
Moe Thi Thi Han1, Nichakorn Satitpornbunpot1, Naoomi Tominaga2
1Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
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.
Insights
Air pollution from biomass burning alters microRNA (miRNA) levels, impacting immune and stress pathways. Diabetes mellitus (DM) modifies these environmental responses, suggesting specific miRNAs as potential biomarkers.
Area of Science:
- Environmental Health
- Molecular Biology
- Biomarker Discovery
Background:
- Seasonal biomass burning in Northern Thailand causes significant fine particulate matter (PM) fluctuations.
- Elevated PM exposure poses health risks, especially for individuals with diabetes mellitus (DM).
- Understanding PM's impact on molecular pathways and potential biomarkers is crucial for public health.
Purpose of the Study:
- To identify circulating microRNAs (miRNAs) responsive to PM exposure.
- To investigate whether metabolic status, specifically DM, modifies these miRNA responses.
- To explore potential roles of these miRNAs as biomarkers for environmental exposure and disease relevance.
Main Methods:
- Small RNA sequencing was performed on plasma samples from a discovery cohort during low- and high-PM periods.
- Quantitative reverse transcription PCR (RT-qPCR) was used to measure specific miRNAs in a longitudinal cohort with and without DM.
- Plasma cytokine levels (IL-8) and exosome concentrations were analyzed.
Main Results:
- Thirteen miRNAs were differentially expressed, with miR-542-3p, miR-29a-3p, novelmiR-203, and novelmiR-754 identified as key candidates.
- In non-DM individuals, PM exposure altered miR-542-3p, miR-29a-3p, and novelmiR-203 levels.
- DM participants exhibited altered baseline miRNA levels and attenuated seasonal responses to PM.
- Plasma IL-8 and exosome concentrations increased during peak PM exposure, indicating inflammation.
- miR-542-3p levels differed between lung cancer patients and healthy controls in an independent cohort.
Conclusions:
- PM exposure significantly alters circulating miRNA, exosomal, and cytokine profiles.
- Diabetes mellitus modifies the systemic response to PM exposure.
- miR-542-3p and miR-29a-3p are promising candidates for environmentally responsive and disease-relevant biomarkers.
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