Fig. 2

Role of lncRNA-mediated HIF, PI3K/AKT/mTOR and LKB1-AMPK pathways in glucose metabolism in tumor cells. LncRNAs can regulate HIF-1α protein synthesis and stability, thus modulating HIF-1-mediated metabolic reprogramming. The rate of translation of HIF-1a mRNA in cancer cells is dependent upon the activity of the mammalian target of rapamycin (mTOR), which in turn is determined by the activity of upstream tumor suppressor proteins and oncoproteins. HIF-1α plays a key role in stimulating glycolic enzymes and in blocking mitochondrial activity. LncRNAs can also regulate Akt and AMPK pathways. Akt may increase oxidative phosphorylation by enhancing metabolic coupling between glycolysis and oxidative phosphorylation, through facilitating the association of mitochondrial hexokinase with VDAC and mitochondria. Akt enhances glycolytic flux via multiple mechanisms. First, it increases glucose uptake and flux. Second, hyperactive Akt activates mTORC1, which promotes HIF1α accumulation under normoxic conditions and increases GLUT1, HKII, and lactate dehydrogenase (LDH) levels. Finally, Akt-increased cellular ATP levels serve to maintain low AMPK activity, which is required for full activation of mTORC1