MicroRNA-184 Increases the Resistance of Gastric Cancer to Cisplatin via PI3K/AKT/mTOR

Abstract

This study sought for investigating the function of miR-184 in resistance of gastric cancer (GC) cells to cisplatin (DDP). Consequently, not only BGC-823 DDP-resistant GC cells (BGC-823/DDP) but also SGC-7901 DDP-resistant cells (SGC-7901/DDP) were upregulated in contrast with their parent cells. Ectopic expressed miR-184 mimetics increased DDP resistance and increased migration as well as invasion in cisplatin-resistant cells. Nevertheless, miR-184 inhibitors reduced DDP resistance, cell invasion as well as migration in parent cells. Besides, Ncor2 is a direct targeting gene for miR-184 in GC cells. Ncor2 gene knockout revealed that DDP resistance promoted cisplatin-resistant cells. Conversely, over Ncor2 expression in BGC-823 cells generated the effect of suppressing resistance to cisplatin. Additionally, over miR-184 expression raised the resistance of cisplatin-resistant cells to DDP, in part arise from the activation of the Ncor2/PI3K/AKT/mTOR signal pathway. miR-184 could also lessen the sensitivity of BGC-823/DDP cells to cisplatin in vivo. To conclude, we evidence that the inactivation of miR-184 or the activation of channel of its target gene can be served as an innovation to reverse DDP resistance in GC.