Coal dust-stimulated macrophage-derived exosomal miR-205-5p promotes thyroid cancer cell phenotypes through CAMK1G-associated NF-kB signaling
Background: Occupational coal dust exposure causes persistent pulmonary inflammation, but the mechanisms by which it may influence thyroid cancer progression remain unclear. Macrophage-derived extracellular vesicles (EVs) may participate in intercellular communication under particulate stress.Objective: This study investigated whether EVs released by coal dust-stimulated macrophages alter thyroid cancer cell behavior and examined the involvement of miR-205-5p, CAMK1G, and NF-kB signaling.Methods: Coal dust was physicochemically characterized before use. EVs were isolated from PMA-differentiated THP-1 macrophages following coal dust exposure and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Small-RNA sequencing, bulk RNA sequencing, TCGA-THCA analysis, and the GSE274674 single-cell dataset were integrated with RT-qPCR, nuclear-cytoplasmic fractionation, dual-luciferase reporter assays, and genetic rescue experiments. Coal dust-exposed C57BL/6J mice and PBMC-humanized NSFG mice bearing TPC-1 xenografts were used for in vivo evaluation.Results: EVs from coal dust-stimulated macrophages were internalized by TPC-1 cells and increased cell viability, clonogenic growth, migration, and invasion while reducing apoptosis. miR-205-5p was enriched in these EVs and accumulated predominantly in the nuclear fraction of recipient cells. Inhibition of miR-205-5p attenuated the EV-associated malignant phenotypes. Integrated transcriptomic analyses prioritized CAMK1G and NF-kB-related signaling. EV treatment increased endogenous CAMK1G expression and the phosphorylation of p65 and IkBa. CAMK1G knockdown reduced these changes, whereas CAMK1G re-expression partially restored the effects suppressed by miR-205-5p inhibition. The reporter assay supported a sequence-dependent interaction between miR-205-5p and the examined CAMK1G 3'-UTR region but did not establish direct positive regulation. In mice, coal dust exposure was associated with pulmonary abnormalities, altered serum FT4 and TPO-Ab levels, increased thyroid CAMK1G expression, and enhanced pulmonary CD206 immunoreactivity. In PBMC-humanized mice, coal dust exposure or experimentally administered macrophage-derived EVs increased xenograft growth, whereas CAMK1G knockdown attenuated tumor burden.Conclusion: These findings support a functional association between coal dust-stimulated macrophage-derived EV signaling and thyroid cancer progression involving miR-205-5p, CAMK1G, and NF-kB-associated activity. However, direct physiological trafficking of endogenous lung-derived EVs to thyroid or tumor tissue was not demonstrated.