Crystalline silica particles exposure modulated miRNA expression profiles in human macrophage-like THP-1 cells

Occupational and environmental exposure to crystalline silica particles is a major global health concern linked to silicosis, pulmonary fibrosis, autoimmune disease, and lung cancer. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and are emerging as potential effect biomarkers of exposure in human biomonitoring studies. To identify intracellular and extracellular miRNAs responses to silica-particle exposure in human THP-1 derived macrophages, differentiated THP-1 derived macrophages were exposed to 0-300 µg/mL crystalline silica particles for 24 h. Cytotoxicity was assessed via LDH release assays. Expression profiles of 24 selected miRNAs were evaluated in intracellular and extracellular compartments, i.e., in cell-suspension and in their conditioned culturing media (secreted exosomes). Significant miRNAs were identified using fold change > ±1.5 and adjusted p < 0.05 (BH method), followed by functional enrichment and correlation analyses. Silica exposure induced dose-dependent cytotoxicity up to 200 µg/mL. Nine intracellular miRNAs (miR-132-5p, miR-1-3p, miR-146a-5p, miR-146b-3p, miR-146b-5p, miR-148a-3p, miR-181a-3p, miR-181c-3p, miR-193a-3p) were significantly modulated; five of these (miR-132-5p, miR-1-3p, miR-146a-5p, miR-148a-3p, miR-193a-3p) were also changed in the secreted exosomes. These five miRNAs showed often non-linear dose-response expression patterns, with bell-shaped or U-shaped trends. Functional enrichment analysis linked these miRNAs to immune activation, inflammatory signaling, and fibrotic pathways, and diseases including silicosis, pulmonary fibrosis, and metabolic disorders. Correlation analyses revealed co-regulation within intracellular and extracellular compartments, with selective miRNA export suggested for miR-193a-3p. In this macrophage model, silica exposure modulates miRNA expression in a non-linear dose-dependent and compartment-specific manner, highlighting intracellular and extracellular miRNAs as potential mechanistic mediators and biomarkers of exposure.