Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:p53 regulates glucose metabolism by miR-34a. 2379 12

Cancer cells metabolize glucose through glycolysis to promote cell proliferation even with abundant oxygen. Multiple glycolysis genes are deregulated during cancer development. Despite intensive effort, the cause of their deregulation remains incompletely understood. Here in this study, we discovered that DHX33 plays a critical role in Warburg effect of cancer cells. DHX33 deficient cells have markedly reduced glycolysis activity. Through RNA-seq analysis, we found multiple critical genes involved in Warburg effect were downregulated after DHX33 deficiency. These genes include lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase muscle isoform 2 (PKM2), enolase 1 (ENO1), ENO2, hexokinase 1/2, among others. With LDHA, PDK1, and PKM2 as examples, we further revealed that DHX33 altered the epigenetic marks around the promoter of glycolytic genes. This is through DHX33 in complex with Gadd45a-a growth arrest and DNA damage protein. DHX33 is required for the loading of Gadd45a and DNA dioxygenase Tet1 at the promoter sites, which resulted in active DNA demethylation and enhanced histone H4 acetylation. We conclude that DHX33 changes local epigenetic marks in favor of the transcription of glycolysis genes to promote cancer cell proliferation. Our study highlights the significance of RNA helicase DHX33 in Warburg effect and cancer therapeutics.
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PMID:Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes. 3261 65