MicroRNA-574-5p directly targets FOXN3 to mediate thyroid cancer progression via Wnt/β-catenin signaling pathway

Objective: Thyroid cancer is the most common endocrine tumor. A large number of thyroid cancer-related miRNAs have been studied and identified. However, the detailed roles of miR-574-5p in thyroid cancer remain poorly understood. This work mainly aimed to investigate the role of miR-574-5p/FOXN3 axis and its mechanism in the thyroid cancer progression.

Methods: MiR-574-5p, FOXN3, Wnt/β-catenin pathway, and apoptosis-related markers were measured by quantitative real-time PCR (qRT-PCR) and western blotting analysis, respectively. Luciferase reporter assay was employed to validate the direct targeting of FOXN3 by miR-574-5p. MTT, flow cytometry, wound healing and transwell experiments were applied to analyze the functions of FOXN3 and miR-574-5p in thyroid cancer cells.

Results: Knockdown of miR-574-5p up-regulated FOXN3 expression and miR-574-5p directly targeted FOXN3 in thyroid cancer cells. Biological function experiments showed that knockdown of miR-574-5p inhibited proliferation, migration, invasion and promoted apoptosis of thyroid cancer cells. The activation of Wnt/β-catenin pathway was suppressed by MiR-574-5p silencing. FOXN3 silencing reversed the effects of miR-574-5p inhibitor on FOXN3 level and Wnt/β-catenin singling pathway, also reversed the effects on cell migration, proliferation, invasion and apoptosis.

Conclusion: The miR-574-5p/FOXN3 axis is a novel molecular mechanism that promotes thyroid cancer progression, suggesting their potential for clinical therapy of thyroid cancer.