MicroRNA-25 contributes to cisplatin resistance in gastric cancer cells by inhibiting forkhead box O3a

Abstract

Gastric cancer (GC) is a common type of malignancy worldwide, and chemotherapeutic resistance accounts for the majority of the failures in clinical treatment. MicroRNAs (miRs) are a class of small non-coding RNAs, which serve essential roles in GC. The present study aimed to investigate the potential role of miR-25 in the cisplatin sensitivity of GC cells. The expression level of miR-25 was significantly upregulated in the cisplatin-resistant GC cell line SGC-7901/DDP compared with the SGC-7901 parental cell line. Overexpression of miR-25 significantly enhanced cell cycle progression and decreased the sensitivity of SGC-7901 cells to cisplatin, whereas inhibition of miR-25 in the SGC-7901/DDP cisplatin-resistant cells resulted in cell cycle arrest at the G0/G1 phase and significantly increased drug sensitivity. Furthermore, the tumor suppressor forkhead box O3a (FOXO3a) was identified as a direct target gene of miR-25 by luciferase assay and western blot analysis, and was shown to mediate the drug-resistance phenotype of GC cells. These findings suggest that upregulation of miR-25 is important for GC cells to establish a cisplatin-resistant phenotype via a FOXO3a-dependent mechanism. Therefore, targeting miR-25 may be a promising therapeutic approach to treat patients with cisplatin-resistant GC.