title: Suppression of lactate dehydrogenase A compromises tumor progression by downregulation of the Warburg effect in glioblastoma.
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.
authors.affiliation: aThe Third Department of Radiotherapy bDepartment of Neurosurgery cThe Fifth Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang dDepartment of Orthopaedics, Boye County Hospital of Hebei Province, Baoding, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Shuchai
authors.initials: S
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Tong
authors.forename: Hui
authors.initials: H
authors.lastname: Hao
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Liu
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005909:Glioblastoma / Q000201:enzymology* / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5