mir-218-2 promotes glioblastomas growth, invasion and drug resistance by targeting CDC27

Oncotarget. 2017 Jan 24;8(4):6304-6318. doi: 10.18632/oncotarget.13850.

Abstract

Glioma has become a significant global health problem with substantial morbidity and mortality, underscoring the importance of elucidating its underlying molecular mechanisms. Recent studies have identified mir-218 as an anti-oncogene; however, the specific functions of mir-218-1 and mir-218-2 remain unknown, especially the latter. The objective of this study was to further investigate the role of mir-218-2 in glioma. Our results indicated that mir-218-2 is highly overexpressed in glioma. Furthermore, we showed that mir-218-2 is positively correlated with the growth, invasion, migration, and drug susceptibility (to β-lapachone) of glioma cells. In vitro, the overexpression of mir-218-2 promoted glioma cell proliferation, invasion, and migration. In addition, the overexpression of mir-218-2 in vivo was found to increase glioma tumor growth. Accordingly, the inhibition of mir-218-2 resulted in the opposite effects. Cell division cycle 27 (CDC27), the downstream target of mir-218-2, is involved in the regulation of glioma cells. Our results indicate that the overexpression of CDC27 counteracted the function of mir-218-2 in glioma cells. These novel findings provide new insight in the application of mir-218-2 as a potential glioma treatment.

Keywords: CDC27; gliomas; invasion; mir-218-2; proliferation.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / genetics
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Drug Resistance, Neoplasm* / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Naphthoquinones / pharmacology*
  • Neoplasm Invasiveness
  • Signal Transduction / drug effects
  • Time Factors
  • Transfection
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CDC27 protein, human
  • MIRN218 microRNA, human
  • MicroRNAs
  • Naphthoquinones
  • beta-lapachone