FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/β-catenin pathway.

Forkhead box N3 (FOXN3) is a subtype of FOX family that has been demonstrated to be implicated in several cancers. However, the role of FOXN3 in papillary thyroid carcinoma (PTC) and its mechanisms have not yet been investigated. Our results showed that FOXN3 was markedly down regulated in PTC tissues and cell lines. Overexpression of FOXN3 suppressed the proliferation, colony formation, migration, and invasion in PTC cells. Overexpression of FOXN3 also prevented EMT process in PTC cells, as shown by the increased E-cadherin expression level and decreased expression levels of N-cadherin and vimentin. In addition, overexpression of FOXN3 inhibited tumor growth of PTC in vivo. Furthermore, overexpression of FOXN3 caused significant decreases in expression levels of β-catenin, c-Myc, and cyclin D1. Additionally, activation of Wnt/β-catenin pathway reversed the effects of FOXN3 on PTC cells. In conclusion, these findings indicated that FOXN3 exerted a tumor suppressive activity in PTC, which was mediated by Wnt/β-catenin pathway.