Cyclin G2 Inhibits the Warburg Effect and Tumour Progression by Suppressing LDHA Phosphorylation in Glioma

Int J Biol Sci. 2019 Jan 1;15(3):544-555. doi: 10.7150/ijbs.30297. eCollection 2019.

Abstract

Cyclin G2 has been identified as a tumour suppressor in several cancers. However, its regulatory roles and underlying mechanisms in tumours are still unknown. In this study, we demonstrated that cyclin G2 was expressed at low levels in glioma, which was as a poor prognostic factor for this disease. We also found that, cyclin G2 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that cyclin G2 plays a tumour suppressive role in glioma. Mechanistically, cyclin G2 could negatively regulate tyrosine-10 phosphorylation of a critical glycolytic enzyme, lactate dehydrogenase A, through direct interaction. Taken together, these results indicate that cyclin G2 acts as a tumour suppressor in glioma by repressing glycolysis and tumour progression through its interaction with LDHA.

Keywords: Warburg effect; cyclin G2; glioma; lactate dehydrogenase A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • Cyclin G2 / genetics
  • Cyclin G2 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • In Situ Nick-End Labeling
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Wound Healing / genetics
  • Wound Healing / physiology*

Substances

  • Cyclin G2
  • L-Lactate Dehydrogenase