Oxidative stress‐responsive microRNA‐320 regulates glycolysis in diverse biological systems

• Published in: The FASEB journal 2012-11, Vol.26 (11), p.4710-4721
• Main Authors: Tang, Huibin, Lee, Myung, Sharpe, Orr, Salamone, Louis, Noonan, Emily J., Hoang, Chuong D., Levine, Sanford, Robinson, William H., Shrager, Joseph B.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenosine Triphosphate - metabolism; Animals; Cell Line; Cloning, Molecular; diaphragm; DNA, Complementary - genetics; Ets; Gene Expression Regulation; Glycolysis - physiology; Humans; Lung Neoplasms - metabolism; mechanical ventilation; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; muscle; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - metabolism; Oxidative Stress - physiology; phosphofructokinase; Phosphofructokinase-1, Muscle Type - genetics; Phosphofructokinase-1, Muscle Type - metabolism; Polymerase Chain Reaction; Proteomics; Research Communications; RNA, Messenger - genetics; RNA, Messenger - metabolism; Warburg effect
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.11-197467

Glycolysis is the initial step of glucose catabolism and is up‐regulated in cancer cells (the Warburg Effect). Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems, and the molecular mechanisms underlying the shifts remain unknown. With proteomics, we observed increased glycolysis in disused human diaphragm muscle. In disused muscle, lung cancer, and H2O2‐treated myotubes, we show up‐regulation of the rate‐limiting glycolytic enzyme muscle‐type phosphofructokinase (PFKm, >2 fold, P150%, P< 0.05). Using microRNA profiling, we identify miR‐320a as a regulator of PFKm expression. Reduced miR‐320a levels (to ~50% of control, P