MiR-146b-5p promotes metastasis and induces epithelial-mesenchymal transition in thyroid cancer by targeting ZNRF3.

BACKGROUND/AIMS: Micro-RNA (miR)-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and associated with extrathyroidal invasion and advanced tumor stage. In the present study, we showed that miR-146b-5p is upregulated in PTC with lymph node metastasis.

METHODS: A computational search and luciferase assay identified zinc RING finger 3 (ZNRF3), a negative regulator of Wnt/β-catenin signaling, as a direct target of miR-146b-5p in PTC.

RESULTS: MiR-146b-5p promoted migration and invasiveness and induced epithelial-mesenchymal transition (EMT) of PTC cells, whereas ZNRF3 overexpression reversed this effect. MiR-146b-5p increased the cell surface levels of the Wnt receptors Frizzled-6 and LRP6 and enhanced Wnt/β-catenin signaling by downregulating ZNRF3, whereas an inhibitor of Wnt/β-catenin suppressed the effect of miR-146b-5p on migration, invasiveness and EMT of PTC cells.

CONCLUSION: These results indicate that miR-146b-5p induces EMT and may promote PTC metastasis through the regulation of Wnt/β-catenin signaling, and suggest novel potential therapeutic targets for the treatment of PTC.