miR-200b is a key regulator of tumor progression and metabolism targeting lactate dehydrogenase A in human malignant glioma

Oncotarget. 2016 Jul 26;7(30):48423-48431. doi: 10.18632/oncotarget.10301.

Abstract

Lactate dehydrogenase A (LDHA) is involved in various cancers. In this study, we investigated the expression and function of LDHA in glioma. We found that LDHA was up-regulated in glioma samples. Furthermore, we found that overexpression of LDHA promoted proliferation, invasion and glycolysis in glioma cells. Luciferase reporter assays confirmed that LDHA was a direct target of miR-200b. miR-200b was found to be down-regulated in glioma samples, which was inversely correlated with LDHA expression. Repression of LDHA by miR-200b suppressed the glycolysis, cell proliferation and invasion of glioma cells. These results provide evidence that miR-200b acts as a tumor suppressor in glioma through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-200b could be a potential therapeutic strategy in glioma.

Keywords: LDHA; glioma; metabolism; miR-200b; proliferation.

MeSH terms

  • Adult
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Glycolysis
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / genetics*
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Luciferases / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness / genetics
  • Up-Regulation

Substances

  • Isoenzymes
  • MIRN200 microRNA, human
  • MicroRNAs
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • Luciferases