MiR-155 affects proliferation and apoptosis of bladder cancer cells by regulating GSK-3β/β-catenin pathway

Z.-C. Dong, D. Zhang, X.-X. Zhang, Z.-Q. Yao, H. Wu, C.-H. Chen, J.-Q. Tian

Department of Urology, Key Laboratory of Gansu Province for Urological Diseases, Department of Urology of Lanzhou University Second Hospital, Urology institute of Lanzhou University Second Hospital, Lanzhou, Gansu, P.R. China. tianjunqiang1@163.com

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• Oncology

OBJECTIVE: GSK-3β negatively regulates Wnt/β-catenin signaling pathway. The abnormal miR-155 expression is associated with bladder cancer. Bioinformatics analysis revealed a complementary binding site between miR-155 and GSK-3β mRNA. This study investigated the role of miR-155 in the proliferation and apoptosis of bladder cancer cells.

PATIENTS AND METHODS: The dual luciferase reporter gene assay validated the targeted regulation between miR-155 and GSK-3β. Tumor tissues and adjacent tissues were collected from bladder cancer patients and the expression of miR-155 and GSK-3β mRNA was detected by RT-PCR. Bladder cancer cell line BIU-87 cells were cultured in vitro and divided into miR-NC group and miR-155 inhibitor group. The expressions of miR-155, GSK-3β and β-catenin were compared, cell apoptosis was detected by flow cytometry, and cell proliferation was detected by EdU staining.

RESULTS: Compared with adjacent tissues, miR-155 expression was significantly increased in bladder cancer tissues, and GSK-3β mRNA expression was significantly decreased. There was a targeted regulatory relationship between miR-155 and GSK-3β. Compared with SV-HUC-1 cells, miR-155 expression in bladder cancer BIU-87 and 5637 cells was significantly increased, and GSK-3β expression was significantly decreased. Transfection of miR-155 inhibitor significantly increased GSK-3β expression in BIU-87 and 5637 cells, decreased β-catenin expression, increased cell apoptosis, and decreased cell proliferation.

CONCLUSIONS: The increased expression of miR-155 plays a role in reducing the expression of GSK-3β and in promoting the pathogenesis of bladder cancer. Inhibition of miR-155 can up-regulate the expression of GSK-3β, inhibit the activity of Wnt/β-catenin pathway, attenuate proliferation and promote apoptosis of bladder cancer cells.

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