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Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma

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 E1α subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphory...

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Autores principales: Sun, Jihong, Li, Jingjing, Guo, Zhixian, Sun, Lu, Juan, Chenghui, Zhou, Yubing, Gu, Hongli, Yu, Yan, Hu, Qiuyue, Kan, Quancheng’, Yu, Zujiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848459/
https://www.ncbi.nlm.nih.gov/pubmed/29444744
http://dx.doi.org/10.3727/096504018X15180451872087
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author Sun, Jihong
Li, Jingjing
Guo, Zhixian
Sun, Lu
Juan, Chenghui
Zhou, Yubing
Gu, Hongli
Yu, Yan
Hu, Qiuyue
Kan, Quancheng’
Yu, Zujiang
author_facet Sun, Jihong
Li, Jingjing
Guo, Zhixian
Sun, Lu
Juan, Chenghui
Zhou, Yubing
Gu, Hongli
Yu, Yan
Hu, Qiuyue
Kan, Quancheng’
Yu, Zujiang
author_sort Sun, Jihong
collection PubMed
description 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 E1α 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.
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spelling pubmed-78484592021-02-16 Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma Sun, Jihong Li, Jingjing Guo, Zhixian Sun, Lu Juan, Chenghui Zhou, Yubing Gu, Hongli Yu, Yan Hu, Qiuyue Kan, Quancheng’ Yu, Zujiang Oncol Res Article 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 E1α 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. Cognizant Communication Corporation 2019-03-29 /pmc/articles/PMC7848459/ /pubmed/29444744 http://dx.doi.org/10.3727/096504018X15180451872087 Text en Copyright © 2019 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Sun, Jihong
Li, Jingjing
Guo, Zhixian
Sun, Lu
Juan, Chenghui
Zhou, Yubing
Gu, Hongli
Yu, Yan
Hu, Qiuyue
Kan, Quancheng’
Yu, Zujiang
Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
title Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
title_full Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
title_fullStr Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
title_full_unstemmed Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
title_short Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma
title_sort overexpression of pyruvate dehydrogenase e1α subunit inhibits warburg effect and induces cell apoptosis through mitochondria-mediated pathway in hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848459/
https://www.ncbi.nlm.nih.gov/pubmed/29444744
http://dx.doi.org/10.3727/096504018X15180451872087
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