Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence has shown that PI3K/Akt pathway is frequently hyperactivated in osteosarcoma (OS) and contributes to tumor initiation and progression. Altered phenotype of glucose metabolism is a key hallmark of cancer cells including OS. However, the relationship between PI3K/Akt pathway and glucose metabolism in OS remains largely unexplored. In this study, we showed that elevated Hexokinase-2 (HK2) expression, which catalyzes the first essential step of glucose metabolism by conversion of glucose into glucose-6-phosphate, was induced by activated PI3K/Akt signaling. Immunohistochemical analysis showed that HK2 was overexpressed in 83.3% (25/30) specimens detected and was closely correlated with Ki67, a cell proliferation index. Silencing of endogenous HK2 resulted in decreased aerobic glycolysis as demonstrated by reduced glucose consumption and lactate production. Inhibition of PI3K/Akt signaling also suppressed aerobic glycolysis and this effect can be reversed by reintroduction of HK2. Furthermore, knockdown of HK2 led to increased cell apoptosis and reduced ability of colony formation; meanwhile, these effects were blocked by 2-Deoxy-d-glucose (2-DG), a glycolysis inhibitor through its actions on hexokinase, indicating that HK2 functions in cell apoptosis and growth were mediated by altered aerobic glycolysis. Taken together, our study reveals a novel relationship between PI3K/Akt signaling and aerobic glycolysis and indicates that PI3K/Akt/HK2 might be potential therapeutic approaches for OS.
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PMID:PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma. 2611 68

Objective To investigate the effect of miR-125b on the aerobic glycolysis of osteosarcoma HOS cells and its underlying mechanism. Methods Real-time quantitative PCR was performed to detect the expression of miR-125b in HOSB normal human osteoblast cells and HOS osteosarcoma cells. The glucose uptake rate was assessed with 3H-2 deoxyglucose (3H-2DG) and lactate production was tested with the kits to observe the effect of miR-125b-mimics on the aerobic glycolysis of osteosarcoma HOS cells. Hexokinase-2 (HK2) protein was detected by Western blot analysis. Dual luciferase reporter gene assay was used to determine whether HK2 was the direct target of miR-125b. Results Compared with HOSB normal human osteoblast cells, the expression of miR-125b was significantly lower in HOS cells. The glucose uptake and lactate production were downregulated in HOS cells transfected with miR-125b-mimics. Aerobic glycolysis of HOS cells was markedly inhibited. Protein level of HK2 was significantly inhibited in HOS cells transfected with miR-125b-mimics. Luciferase assay indicated that HK2 was the direct target of miR-125b. Conclusion miR-125b is down-regulated in HOS cells, and it inhibits the aerobic glycolysis of HOS cells by directly regulating the expression of HK2.
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PMID:[miR-125b suppresses the aerobic glycolysis of osteosarcoma HOS cells by downregulating the expression of hexokinase-2]. 2916 22