pubmed.ncbi.nlm.nih.gov

Role of long non-coding RNAs in glucose metabolism in cancer - PubMed

  • ️Sun Jan 01 2017

Review

Role of long non-coding RNAs in glucose metabolism in cancer

Chunmei Fan et al. Mol Cancer. 2017.

Abstract

Long-noncoding RNAs (lncRNAs) are a group of transcripts that are longer than 200 nucleotides and do not code for proteins. However, this class of RNAs plays pivotal regulatory roles. The mechanism of their action is highly complex. Mounting evidence shows that lncRNAs can regulate cancer onset and progression in a variety of ways. They can not only regulate cancer cell proliferation, differentiation, invasion and metastasis, but can also regulate glucose metabolism in cancer cells through different ways, such as by directly regulating the glycolytic enzymes and glucose transporters (GLUTs), or indirectly modulating the signaling pathways. In this review, we summarized the role of lncRNAs in regulating glucose metabolism in cancer, which will help understand better the pathogenesis of malignant tumors. The understanding of the role of lncRNAs in glucose metabolism may help provide new therapeutic targets and novel diagnostic and prognosis markers for human cancer.

Keywords: Glucose metabolism; LncRNAs; Signaling pathway; Targeted therapy; Warburg effect.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1

LncRNAs regulate the molecules involved in glucose metabolism in cancer. LncRNAs regulate glucose uptake and glycolytic flux by modulating GLUTs and glycolic enzymes

Fig. 2
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

Fig. 3
Fig. 3

Role of lncRNA–mediated Wnt/Snail, STAT and p53 pathways in glucose metabolism in tumor cells. LncRNA can modulate the expression of Wnt/Snail, STAT and p53 expression and exert regulatory effect on glucose metabolism. p53 plays a key role in the process of glycolysis and oxidative phosphorylation, through interacting with various molecules or enzymes, such as TIGAR, GLUTs and PGM, thus affecting several key biological processes including glucose uptake and pyruvate conversion. LncRNAs can affect expression of glycolic enzymes through STAT pathways and modulate mitochondrial activity via Wnt/Snail

Similar articles

Cited by

References

    1. Warburg O. On the origin of cancer cells. Science. 1956;123:309–314. doi: 10.1126/science.123.3191.309. - DOI - PubMed
    1. Warburg O. The chemical constitution of respiration ferment. Science. 1928;68:437–443. doi: 10.1126/science.68.1767.437. - DOI - PubMed
    1. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–1033. doi: 10.1126/science.1160809. - DOI - PMC - PubMed
    1. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006;9:425–434. doi: 10.1016/j.ccr.2006.04.023. - DOI - PubMed
    1. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A. 2007;104:19345–19350. doi: 10.1073/pnas.0709747104. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources