A network toxicology and in vitro study on the role of micro- and nanoplastics in exacerbating the progression risk from Hashimoto's thyroiditis to papillary thyroid carcinoma.

The role of micro-nanoplastics (MNPs) in the elevated risk of papillary thyroid carcinoma (PTC) observed in patients with Hashimoto's thyroiditis (HT) is unclear. We employed an integrated computational and experimental approach to investigate this. By intersecting predicted MNP targets with HT/PTC transcriptomic data, we identified 34 key genes enriched in immune and cancer pathways. Machine learning pinpointed the epigenetic regulator EZH2 as the core driver. Molecular docking and dynamics simulations confirmed stable binding between MNP monomers and EZH2. Intervention with MNPs in vitro HT model significantly upregulated the expression of EZH2, MMP9 and CXCL10, enhanced the levels of pro-inflammatory factors and tumor proliferation marker. Our findings suggest MNPs may contribute to the increased risk of PTC in HT patients via EZH2-mediated epigenetic and inflammatory mechanisms, providing the functional evidence that MNPs can enhance the aggressive potential of thyroid cells under chronic inflammatory conditions.