Background: The incidence of papillary thyroid cancer (PTC) is increasing faster than any other solid tumors worldwide. Invasion and metastasis are the main reasons for the poor prognosis of patients with PTC. Previously, we observed significantly low expression of miRNA-299-5p in invasive PTC tissue samples. 
Aim: The present study aimed to determine whether miR-299-5p plays a key role in PTC migration and invasion. 
Materials and methods: The miR-299-5p expression level was measured using quantitative real-time PCR in 109 human PTC samples and paired adjacent normal tissues and in the human BCPAP PTC cell line. The effects of miR-299-5p on PTC cell migration and invasion were assessed using wound healing and transwell assays. In addition, we searched for the miR-299-5p target, and the potential mechanism was demonstrated using a reporter assay and rescue experiment. 
Results: The expression of miR-299-5p was associated with gender and extrathyroidal extension, and an elevated level of miR-299-5p suppressed BCPAP cell migration and invasion. Estrogen receptor α (ERα) is a direct target of miR-299-5p. The expression level of ERα was significantly higher in PTC tissues and was associated with migration and invasion in PTC cells. Overexpression of ERα could impair miR-299-5p-induced inhibition of migration and invasion. As a key factor of the pathway related to PTC invasion, Gli1 can be combined with ERα and can be regulated by miR-299-5p. 
Conclusion: Our data suggested that miR-299-5p could participate in PTC migration and invasion and could be a potential therapeutic target for patients with aggressive PTC tumors.
Keywords: miR-299-5p, papillary thyroid cancer, PTC, estrogen receptor α, ERα, migration, invasion