Abstract
FoxO3a is a well-defined tumor suppressor gene in the forkhead transcription factor O subfamily (FoxO), and its reduction is related to the occurrence of various tumors. It was found that the expression of miR-155 is abnormally elevated in oral cancer tissues, suggesting that miR-155 may be a tumor-promoting gene for oral cancer. Bioinformatics analysis revealed a targeted complementary binding site between miR-155 and FoxO3a. In this study, we established a cisplatin-resistant cell line of oral cancer to compare the expression of miR-155 and FoxO3a in parental oral cancer cells, and explore whether miR-155 regulates the expression of FoxO3a and affects the proliferation and apoptosis of oral cancer cells. Dual luciferase reporter gene assay validated the targeted regulatory role between miR-155 and FoxO3a. The DDP-resistant oral cancer cell line KB/DDP was established, and the expressions of miR-155 and FoxO3a were compared. The CCK-8 assay was used to calculate the resistance index (RI). KB/DDP cells were divided into miR-NC group and miR-155 inhibitor group. Cell apoptosis was detected by flow cytometry. Cell proliferation ability was detected by EdU staining. There is a targeted regulatory relationship between miR-155 and FoxO3a mRNA. The expression of miR-155 was significantly higher, while the expression of Foxo3a mRNA and protein was obviously lower in KB/DDP cells than that in KB cells. CCK-8 experiments showed that the same concentration of DDP exhibited apparently lower proliferation inhibition in KB/DDP cells than KB cells. Compared with the miR-NC group, transfection of miR-155 inhibitor markedly increased the expression of Foxo3a in KB/DDP cells, which significantly attenuated cell proliferation and enhanced apoptosis in DDP-treated cells. Increased expression of miR-155 and decreased expression of Foxo3a were associated with DDP resistance in oral cancer cells. Inhibition of miR-155 expression upregulated Foxo3a expression, restrained oral cancer cell proliferation, promoted cell apoptosis, and enhanced DDP sensitivity in oral cancer cells.