MiR-146b-5p regulates the scavenging effect of GPx-3 on peroxide in papillary thyroid cancer cells

Background: Glutathione peroxidase (GPx) is an important antioxidant enzyme in thyroid follic-ular cells. Reduced levels of glutathione peroxidase 3 (GPx-3) expression in papillary thyroid cancer (PTC) are associated with poor prognosis. However, the reason for the decreased expression level of GPx-3 in PTC is unclear.Methods: The expression of GPx-3 in papillary thyroid carcinoma and adjacent normal tissue (n = 18) was detected by Western blotting. Bioinformatics was used to predict the relationship be-tween the level of GPx-3 and gender, age, lymph node metastasis, stage, BRAFV600E mutation, and recurrence-free survival of patients. The possible upstream microRNAs of GPx-3 were analyzed by bioinformatics tools also. We verified the relationship between GPx-3 and upstream microRNA by dual luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA).Results: The protein level of GPx-3 decreased in PTC, and analysis of public database datasets suggests that its decreased expression may be associated with the BRAFV600E mutation. MiR-146b-5p was significantly overexpressed in PTC. The dual luciferase reporter assay verified the effect of miR-146b-5p on 3 & PRIME;-UTR of GPx-3 mRNA. Knockdown of miR-146b-5p in thyroid cancer cell lines TPC-1 and BCPAP increased GPx-3 expression levels, accompanied by an increase in the con -version of glutathione (GSH) to oxidized glutathione (GSSG).Conclusions: In conclusion, the level of GPx-3 decreases in papillary thyroid carcinoma and im-pairs intracellular peroxide clearance, due to the inhibitory effect of miR-146b-5p. The accu-mulation of intracellular peroxides may contribute to the poor prognosis of thyroid cancer.