title: Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems.
abstract: 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 H(2)O(2)-treated myotubes, we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase (PFKm, >2 fold, P<0.05) and accumulation of lactate (>150%, 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<0.05) are associated with the increased PFKm in each of these diverse systems. Manipulation of miR-320a levels both in vitro and in vivo alters PFKm and lactate levels in the expected directions. Further, miR-320a appears to regulate oxidative stress-induced PFKm expression, and reduced miR-320a allows greater induction of glycolysis in response to H(2)O(2) treatment. We show that this microRNA-mediated regulation occurs through PFKm's 3' untranslated region and that Ets proteins are involved in the regulation of PFKm via miR-320a. These findings suggest that oxidative stress-responsive microRNA-320a may regulate glycolysis broadly within nature.
authors: Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California 94305-5407, USA.
authors: Huibin
authors: H
authors: Tang
authors: Myung
authors: M
authors: Lee
authors: Orr
authors: O
authors: Sharpe
authors: Louis
authors: L
authors: Salamone
authors: Emily J
authors: EJ
authors: Noonan
authors: Chuong D
authors: CD
authors: Hoang
authors: Sanford
authors: S
authors: Levine
authors: William H
authors: WH
authors: Robinson
authors: Joseph B
authors: JB
authors: Shrager
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D025203:Phosphofructokinase-1, Muscle Type / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D025203:Phosphofructokinase-1, Muscle Type; C026043:PFKM protein, human