@Article{096504018X15180451872087,
AUTHOR = {Jihong Sun, Jingjing Li, Zhixian Guo, Lu Sun, Chenghui Juan, Yubing Zhou, Hongli Gu, Yan Yu, Qiuyue Hu, Quancheng’ Kan, Zujiang Yu},
TITLE = {Overexpression of Pyruvate Dehydrogenase E1a Subunit Inhibits Warburg  Effect and Induces Cell Apoptosis Through Mitochondria-Mediated  Pathway in Hepatocellular Carcinoma},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {4},
PAGES = {407--417},
URL = {http://www.techscience.com/or/v27n4/48553},
ISSN = {1555-3906},
ABSTRACT = {Most cancers rely disproportionately on glycolysis for energy even in the presence of an adequate oxygen 
supply, a condition known as “aerobic glycolysis,” or the “Warburg effect.” Pyruvate dehydrogenase E1 subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphorylation (OXPHOS) 
to aerobic glycolysis and has been suggested to be closely associated with tumorigenesis. Here we observed 
that the PDHA1 protein was reduced in hepatocellular carcinoma (HCC) specimens by immunohistochemistry 
and Western blot, which was significantly associated with poor overall survival. To further analyze the function of PDHA1 in cancer cells, PDHA1 was upregulated in the HCC cell lines SMMC-7721 and HepG2. The 
results demonstrated that overexpression of the PDHA1 gene inhibited aerobic glycolysis with lower lactate via 
increased PDH activity; meanwhile, mitochondrial OXPHOS was enhanced accompanied with higher ATP and 
lower glucose consumption. We also found that apoptosis was promoted and intrinsic pathway proteins were 
increased in PDHA1-overexpressing cells. Collectively, our data indicate that reduced PDHA1 protein expression is associated with the poor clinical outcome of HCC. Upregulated PDHA1 gene expression can inhibit the 
Warburg effect and enhance the mitochondria-mediated apoptosis pathway.},
DOI = {10.3727/096504018X15180451872087}
}