miR-188 Inhibits Glioma Cell Proliferation and Cell Cycle Progression Through Targeting β-Catenin

Oncol Res. 2018 Jun 11;26(5):785-794. doi: 10.3727/096504017X15127309628257. Epub 2017 Dec 21.

Abstract

MicroRNAs (miRNAs) play important roles in several human cancers. Although miR-188 has been suggested to function as a tumor repressor in cancers, its precise role in glioma and the molecular mechanism remain unknown. In the present study, we investigated the effect of miR-188 on glioma and explored its relevant mechanisms. We found that the expression of miR-188 is dramatically downregulated in glioma tissues and cell lines. Subsequent investigation revealed that miR-188 expression was inversely correlated with β-catenin expression in glioma tissue samples. Using a luciferase reporter assay, β-catenin was determined to be a direct target of miR-188. Overexpression of miR-188 reduced β-catenin expression at both the mRNA and protein levels, and inhibition of miR-188 increased β-catenin expression. Moreover, we found that overexpression of miR-188 suppressed glioma cell proliferation and cell cycle G1-S transition, whereas inhibition of miR-188 promoted glioma cell proliferation. Importantly, silencing β-catenin recapitulated the cellular and molecular effects seen upon miR-188 overexpression, which included inhibiting glioma cell proliferation and G1-S transition. Taken together, our results demonstrated that miR-188 inhibits glioma cell proliferation by targeting β-catenin, representing an effective therapeutic strategy for glioma.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Cycle / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics*
  • beta Catenin / biosynthesis*
  • beta Catenin / genetics

Substances

  • CTNNB1 protein, human
  • MIRN188 microRNA, human
  • MicroRNAs
  • beta Catenin