miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells

Cancer Lett. 2013 Jun 10;333(2):253-60. doi: 10.1016/j.canlet.2013.01.039. Epub 2013 Jan 29.

Abstract

Glioblastomas rely mainly on aerobic glycolysis to sustain proliferation and growth; however, little is known about the regulatory mechanisms of metabolism in glioblastoma stem cells. We show that miR-143 is significantly down-regulated in glioma tissues and glioblastoma stem-like cells (GSLCs), while miR-143 over-expression inhibits glycolysis by directly targeting hexokinase 2, and promotes differentiation of GSLCs. Moreover, miR-143 inhibits proliferation of GSLCs under hypoxic conditions and decreases tumor formation capacity of GSLCs in vivo. We also show that a combination of miR-143 and 2-DG, a widely used glycolysis inhibitor, has synergistic effects against GSLCs. miR-143 is a potential therapeutic target for glioblastoma treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / genetics
  • Cell Hypoxia / genetics
  • Cell Line, Tumor
  • Deoxyglucose / pharmacology
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioma / genetics*
  • Glioma / pathology*
  • Glycolysis / genetics
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*
  • Rats

Substances

  • MIRN143 microRNA, human
  • MicroRNAs
  • Deoxyglucose