Cancer cells rely mainly on glycolysis rather than mitochondrial respiration for energy production, which is called the Warburg effect. p53 mutations are observed in about half of cancer cases, and p53 controls the cell cycle and cell death in response to cellular stressors. p53 has been emphasized as a metabolic regulator involved in glucose, glutamine, and purine metabolism. Here, we demonstrated metabolic changes in cancer that occurred through p53. We found that p53-inducible microRNA-34a (miR-34a) repressed glycolytic enzymes (hexokinase 1, hexokinase 2, glucose-6-phosphate isomerase), and pyruvate dehydrogenase kinase 1. Treatment with an anti-miR-34a inhibitor relieved the decreased expression in these enzymes following DNA damage. miR-34a-mediated inhibition of these enzymes resulted in repressed glycolysis and enhanced mitochondrial respiration. The results suggest that p53 has a miR-34a-dependent integrated mechanism to regulate glucose metabolism.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2013 Jul 26|
Bibliographical noteFunding Information:
This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) [National Creative Research Laboratory Program ( 2012R1A3A2048767 ), the Mid-Career Research Program, the National Research Foundation of Korea ( NRF-2007-0056786 & NRF-2010-0007643 ), and the World Class University Program of the MEST and the NRF ( R31-2008-000-10103-0 )], and partly from the National R&D Program for Cancer Control, Ministry of Health & Welfare ( 0720460 ) to H.D.Y.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology