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Surprisingly, all three hexokinase isoforms (HKI, HKII, and HKIII) are significantly downregulated in both ch-ALL subgroups examined compare to healthy bone marrow (all p value >[10.sup.-10]) (Additional file 1: Figure 2a).
(a) Expression of HKII after silencing was measured in REH cells line at the mRNA level (24 h) and (b) at the protein level (48 h).
Analyzing a group of 566 thyroid carcinoma samples they found that the expressionlevels of GLUT1, MCT4, and HKII were associated with cancer aggressiveness and poor prognosis.
Thyroid oncogene Target genes/metabolic pathways Regulation GLUT1, MCT4, HKII, CAIX, Activated [BRAF.sup.V600E] PKM2, GLS1, GDH, ASCT2 [O.sub.2] consumption Inhibited Ras mutations ATP-synthase Inhibited PTEN GLUT1 Activated loss of function p53 mutations GLUT1 Activated Thyroid oncogene Reference [27, 33, 34] [BRAF.sup.V600E]  Ras mutations  PTEN  loss of function p53 mutations [38,39] ASCT2: amino acid transporter-2; CAIX: carbonic anhydrase IX; GLS1: glutaminase; GLUT1: glucose transporter 1; GDH: glutamate dehydrogenase; PKM2: pyruvate kinase isoform M2.
Firstly, miRNAs can directly regulate the expression of genes taking part in glucose uptake and glucose metabolism in GBM, miR-106a regulates GLUT3 , miR-143 regulate HKII , and let-7-a and miR-326 regulate PKM2 [34, 68], which will be detailed in Section 5.
Furthermore, the glycolytic enzyme HKII is targeted by miR-143  which is also found to be downregulated in GBM compared to low WHO grade glioma and normal brain [67, 72].
Furthermore, RAS (specifically N-RAS) is regulated by miR-143 , which also targets the glycolytic enzyme HKII , and by miR-340, which is downregulated in GBM and is associated with poor prognosis [124,125].
Furthermore, miR-143, which is downregulated in GBM [67, 72], has been identified as a direct regulator of HKII in head and neck squamous cell carcinoma (HNSCC) and in colon and lung cancer.
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