Expression of miR-182 and Foxo3a in patients with bladder cancer correlate with prognosis

FoxO3a is a specific tumor suppressor gene in the forkhead transcription factor O subfamily (FoxO). Studies show that its expression plays a role in bladder cancer. The abnormal expression of miR-182 in bladder cancer suggests that miR-182 may be an oncogene in bladder cancer. Bioinformatic analysis showed that there is a target complementary binding site between miR-182 and Foxo3a. In this study, the expression of miR-182 and Foxo3a in cancer tissues of patients with bladder cancer was detected. The expression of miR-182 and Foxo3a in bladder cancer tissues and their relationship with the prognosis of the patients were analyzed, and the role of miR-182 in regulating the expression of Foxo3a and the biologic process of cell proliferation and apoptosis in bladder cancer cells was explored.

Tumor tissues of patients with bladder cancer were collected and the normal bladder mucosa was used as a control. The expression of Foxo3a was detected by western blot. The expression of miR-182 and Foxo3a mRNA was detected by qRT-PCR. The relationship between miR-182, Foxo3a mRNA and the clinical features of patients was analyzed. The median expression of miR-182 and Foxo3a mRNA was bounded, and Log Rank test was used to compare the survival rate of low and high expression of miR-182 and Foxo3a mRNA. The double luciferase reporter gene assay was used to confirm a target regulatory effect between miR-182 and Foxo3a. In vitro, RT112 and T24 cells were divided into 2 groups: group miR-NC, and group miR-182 inhibitor. qRT-PCR and western blot were used to detect the expression of Foxo3a, flow cytometry was used to detect cell apoptosis, and EdU staining was used to detect cell proliferation.

Compared with normal bladder tissue, the expression of miR-182 in bladder cancer tissue was significantly increased, and it was related to tumor size, TNM stage, and lymph node metastasis (P < 0.05). The expression of Foxo3a mRNA was significantly decreased, and was related to tumor size, TNM stage, histopathologic classification, and lymph node metastasis (P < 0.05). There was a significant negative correlation between the expression of miR-182 and Foxo3a mRNA in bladder cancer (r = -0.602, P < 0.05). The prognosis of patients with high expression of miR-182 was significantly worse than that of those with low miR-182 expression. The prognosis of patients with low expression of Foxo3a was significantly better than those with high Foxo3a. Double luciferase reporter gene experiments confirmed that there was a target regulatory relationship between miR-182 and Foxo3a. Transfection of miR-182 inhibitor significantly increased the expression of Foxo3a in RT112 and T24 cells, significantly reducing cell proliferation, and significantly increasing apoptosis.

The expression of miR-182 was increased and the expression of Foxo3a was decreased in bladder cancer, which is related to prognosis. Downregulation of the expression of miR-182 can increase the expression of Foxo3a, inhibiting the proliferation of bladder cancer cells and inducing apoptosis.