Modulation of cell migration and invasion of thyroid cancer cells using miRNA-enriched extracellular vesicles

Extracellular vesicles (EVs) have been investigated as promising vehicles for delivering drugs and microRNAs (miRNAs) in distinct types of cancer. However, their use as a delivery system in papillary thyroid carcinoma (PTC) remains underexplored. PTC is the most prevalent subtype of thyroid cancer, and despite its good prognosis, a fraction of the cases evolve into aggressive and fatal forms. Here, we investigated whether non-tumor thyroid cells can be engineered to produce EVs-enriched with tumor suppressor miRNAs that could be delivered to PTC cells.

EVs from NThy-ORI cells transfected with miR-485-5p or miR-495-3p were isolated by differential ultracentrifugation and characterized by Nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western Blot. Functional in vitro assays were conducted to explore the impact of miRNA-enriched EVs on PTC progression.

Non-tumor thyroid NThy-ORI cells overexpressing miR-485-5p or miR-495-3p efficiently produced EVs enriched with these miRNAs, which were internalized by PTC cells. Treatment with miRNA-enriched EVs modulated the expression of validated miRNA targets and key epithelial-mesenchymal transition-related genes, leading to a 40% reduction in migration (p<0.0001) and a 60% reduction in invasion in both miRNAs and cell lines tested (p<0.001).

These findings suggest the potential of thyroid-derived EVs as a biologically relevant and promising system for delivering tumor suppressor miRNAs, opening new opportunities to explore this approach as a therapeutic strategy for PTC.