MiR-183 maintains canonical Wnt signaling activity and regulates growth and apoptosis in bladder cancer via targeting AXIN2

Eur Rev Med Pharmacol Sci. 2018 Aug;22(15):4828-4836. doi: 10.26355/eurrev_201808_15618.

Abstract

Objective: Previous investigations have shown that miR-183 is upregulated in bladder cancer (BC); however, its biological significance is not fully investigated. The goal of the current study is to analyze the function of miR-183 in BC development and progression.

Patients and methods: 23 pairs of BC tumor and adjacent tissues were analyzed for miR-183 and c-Myc expression using Real-time polymerase chain reaction (PCR). MiR-183 expression was modulated by transfection of miR-183 or miR-183 inhibitor (miR-183-in). Protein expression of AXIN2, c-Myc and Cyclin D1 was determined by western blot. Cell growth activity and apoptotic potential were evaluated by cell viability assay and flow cytometry assay, respectively. Luciferase activity assay was conducted to determine whether AXIN2 is a direct target of miR-183.

Results: The expression of miR-183 is upregulated in BC tissues and cell lines, and is positively correlated with the expression of the Wnt target gene, c-Myc. MiR-183 positively regulated Wnt signaling activity by directly suppressing its negative feedback regulator, AXIN2. Overexpression of miR-183 promoted cell growth and inhibited apoptosis. Inhibition of miR-183 attenuated cell growth and enhanced apoptosis. The effect of miR-183 on cell growth and apoptosis can be abolished by knockdown of AXIN2.

Conclusions: MiR-183 functions as an oncomiR in BC and upregulates Wnt signaling activity by directly suppressing AXIN2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Axin Protein / antagonists & inhibitors
  • Axin Protein / biosynthesis*
  • Axin Protein / genetics
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Wnt Signaling Pathway / physiology*

Substances

  • AXIN2 protein, human
  • Axin Protein
  • MIRN183 microRNA, human
  • MicroRNAs