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

Pathol Res Pract. 2020 Jun;216(6):152939. doi: 10.1016/j.prp.2020.152939. Epub 2020 Mar 31.


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.

Keywords: FOXN3; MiRNA-574-5p; Thyroid cancer; Wnt/β-catenin pathway.

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Wnt Signaling Pathway / genetics*


  • Cell Cycle Proteins
  • FOXN3 protein, human
  • Forkhead Transcription Factors
  • MIRN574 microRNA, human
  • MicroRNAs