Table 1.
ncRNAs and their participation in cancer metabolic processes through oncogenic or tumor suppressor pathways.
| Pathway | ncRNA | Biological activity | Cancer | References |
|---|---|---|---|---|
| PI3K/AKT signaling: leads to an increase in HIF-1α and thus, enhances the expression of glycolytic enzymes (LDH-B, PKM2, GLUT1; Zha et al., 2011). | miR-126 | Targets the p85b subunit of PI3K. | CC, gastric, BRCA. | Guo et al., 2008; Feng et al., 2010; Zhou et al., 2014 |
| miR-199 | Repress mTOR1 and c-met. | HCC | Guo et al., 2008; Fornari et al., 2010 | |
| miR-21 | Activates PI3K/AKT/mTOR pathway. | BLACA | Yang et al., 2015 | |
| miR-181a | Induces a metabolic shift by inhibiting the expression of PTEN, leading to an increase in phosphorylated Akt. | CC | Wei et al., 2014 | |
| Akt: stimulates glycolysis by increasing expression of glucose transporters and glycolytic enzymes | miR-451 | Regulates AMPK signaling in response to glucose levels by targeting the binding partner of LKB1, CAB39 (MO25a). | GC | Elstrom et al., 2004; Godlewski et al., 2010 |
| IGF-I/insulin signaling: increased expression of genes involved in the regulation of glucose metabolism and mitochondrial function | miR-7 | Inhibits cellular growth and glucose metabolism by regulating the IGF-1R/Akt signaling pathway. | GC | Wang B. et al., 2014 |
| miR-126 | Negatively regulates IRS1, an adaptor protein mediating IGF-I/insulin signaling, leading to activation of the PI3K, Akt and Ras-MAPK pathways. | Mesothelioma, HCC | Ryu et al., 2011; Tomasetti et al., 2014 | |
| miR-33a/b | Controls the expression of Irs2 affecting Akt phosphorylation. Also, represses AMP-activated kinase 1 (Ampkα1) and sirtuin 6 (Sirt6), involved in the regulation of lipid and glucose metabolism. | BRCA | Davalos et al., 2011 | |
| c-Myc: The oncogene deregulates glycolysis through the activation of several components of the glucose metabolic pathway. | miR-23 | c-Myc transcriptionally represses miR-23a/b, which targets glutaminase (GLS) inducing mitochondrial dysfunction. | Lymphoma and PCA | Gao et al., 2009 |
| lncRNA PCGEM1 | Stimulates the uptake of glucose by aerobic glycolysis and interacts directly with c-Myc, and enhances its transactivation activity by its recruitment to chromatin. | PCA | Dang et al., 2009; Hung et al., 2014 | |
| HIF signaling: key transcription factor mediating responses to hypoxia, and HIF-target genes, implicated in deregulated tumor metabolism. | miR-199a and miR-125b | Directly targets HIF-1α and other miRNAs, enhancing tumor angiogenesis. | OC | He et al., 2013 |
| miR-424 | Hypoxia-inducible miRNA, that targets cullin (CUL2), which stabilizes HIF-1α. | OC (endothelial cells) | Ghosh et al., 2010 | |
| miR-17-92 | Down-regulates HIF-1α, leading to evasion of apoptosis. | LC | Taguchi et al., 2008 | |
| miR-451 | Reduces activation of the LKB1/AMPK pathway, facilitating unrestrained mTOR activity. | GB | Godlewski et al., 2010 | |
| P53: Its down-modulation provides a selective advantage for cancer cells by increasing glycolysis. | miR-34 | Loss of its expression interrupts p53/miR34 feedback resulting in lower activity of both molecular actors, leading to the over-expression of glycolytic enzymes (HK1/2, GPI, and PDH1). | Most tumors | Voorhoeve et al., 2007; Kumar et al., 2011; Kim et al., 2013 |
| miR-25, 30d, 504, and 125b | Directly target p53 and impairs p53 response. | Gastric, brain and LC | ||
| miR-372 and 373. | Neutralizes p53-mediated CDK inhibition, by silencing LATS2. | Testicular germ cell tumors | ||
| lncRNA MEG3 | Down-modulation of MEG3 disturbs the activation of MDM2 and p53. | Non-small cell LC | Lu et al., 2013 |
LC, lung cancer; HCC, hepatocellular carcinoma; BlaCa, Bladder cancer; CC, colon cancer; BRCA, breast cancer; PCA, prostate cancer; GC, glioblastoma cancer.