Circulating myeloid-derived suppressor cells facilitate invasion of thyroid cancer cells by repressing miR-486-3p.
2020
BACKGROUND Myeloid-derived suppressor cells (MDSCs) have become increasingly recognized as facilitators of tumor development. However, the role of MDSCs in papillary thyroid carcinoma (PTC) progression has not been clearly explored. OBJECTIVE: We aimed to evaluate the levels as well as function of circulating MDSCs in PTC. METHODS The proportion of circulating PMN-MDSCs and M-MDSCs from patients with PTC or benign thyroid nodules and healthy controls was measured using flow cytometry. For immunosuppressive activity analysis, sorted circulating MDSCs were co-cultured with CD3/CD28-costimulated T lymphocytes and the proliferation of T cells was determined. PTC cell lines (TPC-1 and BC-PAP) were co-cultured with PMN-MDSCs, and the effects on cell migration, invasion, proliferation and apoptosis were evaluated. The differential expressed miRNAs and mRNAs and their function were also explored in TPC-1 cells cocultured with or without PMN-MDSCs. RESULTS PMN-MDSCs were increased in the peripheral blood mononuclear cells (PBMC) of patients with PTC. Circulating PMN-MDSCs displayed strong T cell suppressive activity. PTC cells demonstrated enhanced invasive capabilities in vitro and in vivo when co-cultured with sorted PMN-MDSCs. PMN-MDSCs decreased expression of miR-486-3p and activated NF-κB2, a direct target of miR-486-3p. Rescue of miR-486-3p diminished the cell migration and invasion induced by PMN-MDSCs. CONCLUSION Collectively, our work indicates that circulating PMN-MDSCs promote PTC progression. By suppressing miR-486-3p, PMN-MDSCs promote the activity of the NF-κB2 signaling pathway, resulting in accelerated invasion of PTC cells, which may provide new therapeutic strategies for treatment of thyroid cancer.
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