Circulating miR-126 and miR-155 are associated with environmental lead exposure: A translational approach via human biomonitoring and bioinformatic networks

Exposure to environmental contaminants, particularly lead (Pb), has increased due to anthropogenic activities and has been associated with epigenetic alterations, including changes in microRNA (miRNA) expression. Certain miRNAs have emerged as potential biomarkers of environmental exposure and early biological effects. Among them, miR-126 and miR-155 have been reported to be responsive to lead exposure. In this exploratory study, we evaluated circulating levels of miR-126 and miR-155 in a Mexican population environmentally exposed to lead and performed bioinformatic analyses to investigate the biological pathways potentially regulated by these miRNAs. Our results showed a mean blood lead concentration of 7.6 ± 5.8 μg/dL, with more than 50 % of participants exceeding the Mexican reference value (≥5 μg/dL; NOM-199-SSA1-2000). Both miRNAs showed significantly altered expression patterns associated with elevated blood lead levels (p < 0.05). Gene Ontology and KEGG pathway analyses of predicted target genes revealed enrichment in pathways related to inflammation, angiogenesis, lipid metabolism, and atherosclerosis, including AGE-RAGE signaling, TNF, Toll-like receptor, and fluid shear stress-related pathways. Protein-protein interaction network analysis identified MYC as a shared regulatory node, suggesting coordinated regulation of biological processes relevant to cardiovascular function. Together, these findings indicate that lead exposure is associated with altered circulating miR-126 and miR-155 expression and with modulation of pathways related to cardiovascular health. Although causal inferences cannot be drawn due to the observational design, these results provide a framework for future large-scale epidemiological and functional studies aimed at elucidating epigenetic responses to environmental lead exposure.