MiR-574-5p mediates the cell cycle and apoptosis in thyroid cancer cells via Wnt/β-catenin signaling by repressing the expression of Quaking proteins

Oncol Lett. 2018 Apr;15(4):5841-5848. doi: 10.3892/ol.2018.8067. Epub 2018 Feb 15.

Abstract

Thyroid cancer is the most frequently occurring type of endocrine tumor, with a rapidly increasing incidence rate. MicroRNA (miR)-574-5p is a candidate oncogene in various types of cancer. The present study identified that miR-574-5p affected the cell cycle distribution and apoptosis of BCPAP and FTC133 thyroid cancer cells via β-catenin/Wnt signaling by targeting Quaking proteins (QKIs). An MTT assay demonstrated that the knockdown of miR-574-5p suppressed the proliferation of the thyroid cancer cells. Fluorescence-activated cell sorting analysis demonstrated that the inhibition of miR-574-5p induced the G1/S phase arrest and apoptosis of the cells. Reverse transcription-quantitative polymerase chain reaction and western blot analyses revealed that the knockdown of miR-574-5p significantly upregulated the mRNA and protein expression levels of QKIs. Furthermore, western blot analysis identified that the knockdown of miR-574-5p also repressed the Wnt/β-catenin pathway via downregulating the expression of β-catenin, cyclin D1 and survivin, and upregulating the phosphorylation of β-catenin. The further depletion of QKIs in combination with the knockdown of miR-574-5p not only increased the expression of β-catenin, cyclin D1 and survivin, but also rescued the apoptosis of thyroid cancer cells induced by the miR-574-5p knockdown. In conclusion, these findings indicated that the aberrant upregulation of miR-574-5p may be oncogenic, through regulating the Wnt/β-catenin pathway by targeting QKIs.

Keywords: Quaking proteins; Wnt/β-catenin signaling; apoptosis; cell cycle; microRNA-574-5p; thyroid cancer.