miR-199b-5p-Stonin 2 axis regulates metastases and epithelial-to-mesenchymal transition of papillary thyroid carcinoma

Abstract

Papillary thyroid carcinoma is one of the most fatal malignant endocrine tumors, and the prognosis remains poor because of the lack of effective therapeutic targets. In this study, we demonstrated that the level of miR-199b-5p was markedly downregulated in papillary thyroid carcinoma. The ectopic expression level of miR-199b-5p in papillary thyroid carcinoma cell B-CPAP could inhibit growth, migration, and invasion as well as epithelial-mesenchymal transition (EMT) and decreased cell metastasis in vivo, but silencing miR-199b-5p caused a contradictory outcome. Additionally, Stonin 2 (STON2) was identified as a direct target gene of miR-199b-5p. Consistent with the downregulation of miR-199b-5p, the overexpression of STON2 induced the growth, migration and invasion of B-CPAP cells. It was also demonstrated that miR-199b-5p suppressed papillary thyroid carcinoma cell aggressiveness by targeting STON2. Furthermore, the overexpression of miR-199b-5p inhibited cell proliferation, promoted apoptosis, and increased the chemo-sensitivity of thyroid carcinoma B-CPAP cells toward the chemotherapy drug paclitaxel. Finally, in vivo experiments further demonstrated that miR-199b-5p suppressed tumor growth in nude mice. Thus, this study revealed that miR-199b-5p functions as antioncogene miRNA in papillary thyroid carcinoma cells and that the miR-199b-5p/STON2 axis might be a potential treatment option for papillary thyroid carcinoma. © 2018 IUBMB Life, 71(1):28-40, 2019.

Keywords: STON2; metastasis; miR-199b-5p; papillary thyroid carcinoma.