Expression of microRNA-124 in bladder cancer and its clinical significance

• Main Authors: WANG Yang, HU Yueshi, LI Zheng, ZHU Qing, DUAN Qixin
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2020-05-01
• Series: Di-san junyi daxue xuebao
• Subjects: bladder cancer; microrna-124; cell proliferation; akt signaling pathway
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/201912083.htm

Objective To investigate the expression of microRNA-124 (miR-124) in bladder cancer and its clinical significance. Methods The expression of miR-124 in a normal bladder urothelial cell line (SV-HUC-1) and 5 bladder cancer cell lines (5 637, J82, T24, TCCSUP and UM-UC-3) was detected using RT-qPCR. We also detected the expression of miR-124 using in situ hybridization in 114 tissue specimens of bladder cancer and adenocarcinoma tissues from patients undergoing surgeries in our hospital between January, 2013 and January, 2016. The correlations of miR-124 expression with the clinicopathological characteristics and prognosis of the patients were analyzed. In the in vitro experiment, we tested the effect of transfection with miR-124 mimics and miR-124 inhibitor on the proliferation of bladder cancer T24 cells using CCK-8 assay and on the cellular expression of PCNA, Ki-67 and p-AKT using Western blotting. Results The expression of miR-124 in the 5 bladder cancer cell lines was significantly lower than that in normal bladder urothelial cells. The results of in situ hybridization showed that miR-124 was highly expressed in normal bladder urothelial cells but lowly expressed in non-invasive and invasive bladder cancer tissues. The expression of miR-124 was closely correlated with clinical T stage (Chi-square=6.829, P=0.009), lymph node metastasis (Chi-square= 6.844, P=0.009) and tumor differentiation (Chi-square=5.111, P=0.024). Kaplan-Meier analysis showed that compared with those with a high expression of miR-124, the patients with a low expression of miR-124 had significantly shorter overall survival (Chi-square=22.7, P < 0.01) and disease-free survival (Chi-square=26.57, P < 0.01). Multivariate analysis showed that a low expression of miR-124 was an independent risk factor for a poor prognosis in patients with bladder cancer in terms of both the overall survival (HR=4.63, 95% CI: 1.39~7.23; P=0.007) and disease-free survival (HR=5.82, 95% CI: 1.56~11.42; P=0.003). In the cell experiment, transfection with the miR-124 mimics significantly attenuated the proliferation of T24 cells (P < 0.05) and lowered the expressions of proliferation-related proteins (PCNA, Ki-67) and p-AKT as compared with the negative control (P < 0.05), while transfection with the miR-124 inhibitor resulted in the reverse changes (P < 0.05). Conclusion The low expression of miR-124 in bladder cancer cells and tissues can promote cancer cell proliferation and is associated with a poor prognosis of the patients possibly in relation with the activation of AKT signaling pathway.