Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4

Cancer Lett. 2012 Aug 1;321(1):45-54. doi: 10.1016/j.canlet.2012.03.013. Epub 2012 Mar 16.

Abstract

Many tumors metabolise the majority of the glucose that they take up through glycolysis even in the presence of an adequate oxygen supply. Lactate dehydrogenase A (LDH-A) is the critical enzyme that catalyses the transformation of pyruvate to lactate. We demonstrate that LDH-A reduction can suppress the tumorigenicity of intestinal-type gastric cancer (ITGC) cells by downregulating Oct4 both in vitro and in vivo. A statistical analysis of 661 ITGC specimens showed a significant correlation between LDH-A and Oct4 expression. Moreover, patients with low LDH-A/negative Oct4 expression exhibited better overall survival than patients with other combinations. We conclude that the close correlation of LDH-A and Oct4 may offer a promising therapeutic strategy for ITGC.

MeSH terms

  • Cell Line, Tumor
  • Down-Regulation
  • Histone Deacetylase 1 / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • L-Lactate Dehydrogenase / metabolism*
  • Lactate Dehydrogenase 5
  • Lentivirus / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Prognosis
  • RNA, Small Interfering / pharmacology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology

Substances

  • Isoenzymes
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • HDAC1 protein, human
  • Histone Deacetylase 1