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Suppression of lactate dehydrogenase A compromises tumor progression by downregulation of the Warburg effect in glioblastoma - PubMed

  • ️Fri Jan 01 2016

Suppression of lactate dehydrogenase A compromises tumor progression by downregulation of the Warburg effect in glioblastoma

Juan Li et al. Neuroreport. 2016.

Abstract

Reprogrammed glucose metabolism is an emerging hallmark of cancer cells, which show a unique metabolic phenotype known as the Warburg effect. Lactate dehydrogenase A (LDHA), a key enzyme in the glycolytic process, executes the final step by conversion of lactate into pyruvate. However, little is known about the roles of LDHA in human glioblastoma (GBM). In this study, we aimed to determine the effects of LDHA and elucidate related underlying mechanisms. Data derived from Oncomine database showed that LDHA is commonly upregulated in GBM tissues in comparison with corresponding normal controls. Silencing of LDHA expression resulted in reduced glycolysis, decreased cell growth, increased cell apoptosis, and attenuated invasive ability. In the presence of 2-deoxyglucose, a glycolysis inhibitor, the oncogenic activities of LDHA were completely blocked. These findings provide evidence of the cellular functions of LDHA in the progression of GBM and suggest that LDHA might act as a potential therapeutic target for GBM treatment.

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Figures

Fig. 1
Fig. 1

LDHA expression is upregulated in GBM tissues. The mRNA expression of LDHA in Oncomine datasets including Lee brain (a), Shai brain (b), Sun brain (c), and Liang brain (d), as well as TCGA brain (e) is upregulated in GBM tissues compared with the normal control tissues. GBM, glioblastoma; LDHA, lactate dehydrogenase A.

Fig. 2
Fig. 2

Silencing of LDHA compromises tumor growth and invasion in GBM cells. (a) Interfere efficiency of LDHA in A172 and U87 cells as shown by western blotting. (b) Representative photograph of culture medium in si-LDHA and si-Ctrl cells. Lactate production (c) and glucose utilization (d) in GBM cells were reduced after LDHA was silenced. Cell colony formation assay (e), cell apoptosis assay (f), and Transwell assay (g) were performed to detect cell proliferation ability, caspase-3/7 activity, and cell invasive ability in si-LDHA and si-Ctrl cells, respectively. LDHA-silenced cells showed decreased cell proliferation ability and invasive ability, and enhanced caspase-3/7 activity compared with si-Ctrl cells. Scale bar: 50 μm; si-Ctrl versus si-LDHA; *P<0.05; **P<0.01. GBM, glioblastoma; LDHA, lactate dehydrogenase A.

Fig. 3
Fig. 3

The oncogenic roles of LDHA are dependent on an enhanced Warburg effect. (a) Representative photograph of culture medium in si-LDHA and si-Ctrl cells in the presence of 2-DG. Effects of silencing of LDHA on cell growth as shown by colony formation assay (b), cell apoptosis as measured by caspase-3/7 activity, (c) and cell invasion as shown by the Transwell model (d) in A172 and U87 cells were measured. In the presence of 2-DG, the effects of LDHA on cell growth, cell apoptosis, and cell invasion were completely blocked. Scale bar: 50 μm; si-Ctrl versus si-LDHA; *P<0.05; **P<0.01. 2-DG, 2-deoxyglucose; GBM, glioblastoma; LDHA, lactate dehydrogenase A.

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