miR-124 suppresses glioblastoma growth and potentiates chemosensitivity by inhibiting AURKA

Biochem Biophys Res Commun. 2017 Apr 22;486(1):43-48. doi: 10.1016/j.bbrc.2017.02.120. Epub 2017 Feb 24.

Abstract

Glioblastoma (GBM) accounts for about half of all malignant brain cancers. Although the treatment strategies for glioblastoma develop rapidly, a considerable number of patients could not benefit from temozolomide (TMZ)-based chemotherapy. Here, we revealed a miR-124-AURKA axis that regulated glioblastoma growth and chemosensitivity. Mechanistically, AURKA was up-regulated in glioblastoma tissues and associated with poor overall survival. While overexpression of AURKA enhanced tumor growth, genetic or pharmacological inhibition of AURKA led to growth-inhibitory and chemopotentiating effects in glioblastoma. AURKA was further identified as a target of miR-124. Furthermore, our data showed that miR-124 down-regulated AURKA expression and subsequently suppressed cell growth. Re-expression of AURKA significantly rescued miR124-mediated proliferation repression and chemosensitivity. In conclusion, our results demonstrated that miR-124 inhibited glioblastoma growth and potentiated chemosensitivity by targeting AURKA, which may represent promising targets and rational therapeutic options for glioblastoma.

Keywords: AURKA; Glioblastoma; Temozolomide (TMZ); miR-124.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase A / genetics*
  • Aurora Kinase A / metabolism
  • Azepines / administration & dosage
  • Base Sequence
  • Blotting, Western
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Pyrimidines / administration & dosage
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Temozolomide
  • Tumor Burden / drug effects
  • Tumor Burden / genetics
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • Azepines
  • MIRN124 microRNA, human
  • MLN 8237
  • MicroRNAs
  • Pyrimidines
  • Dacarbazine
  • AURKA protein, human
  • Aurora Kinase A
  • Temozolomide