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

Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5682-5690. doi: 10.26355/eurrev_201907_18305.

Abstract

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.

Publication types

  • Retracted Publication

MeSH terms

  • Antagomirs / metabolism
  • Apoptosis*
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / chemistry
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Sequence Alignment
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / metabolism

Substances

  • Antagomirs
  • MIRN155 microRNA, human
  • MicroRNAs
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta