MicroRNA-338-3p inhibits thyroid cancer progression through targeting AKT3.

microRNA-338-3p (miR-338-3p) has been implicated in tumor development and progression in many types of cancers. However, the function and mechanism underlying the action of miR-383-3p in thyroid cancer remain unclear and were therefore investigated in this study by in vitro and in vivo experiments. We found that miR-338-3p was downregulated in thyroid cancer tissues and cell lines. miR-338-3p expression was significantly associated with the clinical stage and lymph node metastasis of thyroid cancer. Forced expression of miR-338-3p suppressed thyroid cancer cell proliferation, clonogenicity, migration, and invasion in vitro and inhibited tumorigenesis in a nude mouse xenograft model system. Moreover, AKT3, a known oncogene, was confirmed as a direct target of miR-383-3p in thyroid cancer cells, as evidenced by the fact that ectopic miR-383 expression suppressed AKT3 expression and its downstream pathway (AKT pathway). In addition, AKT3 silencing by siRNA mimicked the effect of ectopic miR-338-3p on the growth and invasion of thyroid cancer cells. In contrast, AKT3 overexpression attenuated the inhibitory effect induced by miR-338-3p overexpression in thyroid cancer cells. These results suggest that miR-338-3p functions as a novel tumor suppressor that blocks thyroid cancer cell growth through targeting AKT3.