MiR-338 suppresses cell proliferation and invasion by targeting CTBP2 in glioma

Cancer Biomark. 2017 Sep 7;20(3):289-297. doi: 10.3233/CBM-170128.

Abstract

Background: Previous studies indicated that microRNA-338-5p (miR-338-5p) functions as tumor suppressor in some cancer types including glioma. However, the clinical significance and biological function of miR-338-5p in glioma still need to be explored.

Methods: We used quantitative real time PCR (qRT-PCR) to detect the miR-338-5p expression in the 44 cases of glioma tissues and adjacent normal tissues. In vitro, CCK8 cell proliferation, cell colony formation, transwell invasion assay and flow cytometry analysis were performed to explore the effects of miR-338-5p on cell proliferation, cell invasion and cell cycle distribution. Dual luciferase assay, qRT-PCR and western blot analysis were applied to validate CTBP2 was a direct target of miR-338-5p in glioma cells.

Results: we demonstrated that miR-338-5p was significantly lower expression in 44 glioma patients, compared with adjacent normal tissues. MiR-338-5p expression was significantly correlated with glioma grades and Karnofsky Performance Status in patients. We then validated that increased miR-338-5p significantly inhibited the cell proliferation, cell invasion and epithelial-mesenchymal transition (EMT) in vitro. Moreover, Dual luciferase assay results indicated that CTBP2 was direct target of miR-338-5p in glioma cells. Meanwhile, CTBP2 silencing can rescued the phenotype changes induced by miR-338-5p inhibitor on cell proliferation and invasion in glioma.

Conclusion: Our results suggested that miR-338-5p acts as tumor suppressor and could be a potential therapeutic target for glioma.

Keywords: CTBP2; Glioma; cell invasion; cell proliferation; miR-338-5p.

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Co-Repressor Proteins
  • Down-Regulation
  • Female
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Transfection

Substances

  • Co-Repressor Proteins
  • MIRN338 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • Alcohol Oxidoreductases
  • CTBP2 protein, human