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Oxidative stress‐responsive microRNA‐320 regulates glycolysis in diverse biological systems
Author(s) -
Tang Huibin,
Lee Myung,
Sharpe Orr,
Salamone Louis,
Noonan Emily J.,
Hoang Chuong D.,
Levine Sanford,
Robinson William H.,
Shrager Joseph B.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-197467
Subject(s) - glycolysis , warburg effect , phosphofructokinase , microrna , regulator , microbiology and biotechnology , oxidative stress , chemistry , oxidative phosphorylation , myogenesis , downregulation and upregulation , biology , biochemistry , enzyme , myocyte , gene
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.—Tang, H., Lee, M., Sharpe, O., Salamone, L., Noonan, E. J., Hoang, C. D., Levine, S., Robinson, W. H., Shrager, J. B. Oxidative stress‐responsive microRNA‐320 regulates glycolysis in diverse biological systems. FASEB J. 26, 4710–4721 (2012). www.fasebj.org