Skip to main content
SpringerLink
Log in

MicroRNAs and Cancer Metabolism

  • Chapter
  • First Online:
MicroRNAs in Cancer Translational Research

Abstract

Over 80 years ago, Otto Warburg discovered the phenomena of aerobic glycolysis, known now as the Warburg effect, whereby cancer cells relies on glycolysis, rather than the more efficient process of oxidative phosphorylation, for ATP production, even when oxygen is available. Recent progress in the field of cancer metabolism documents that alterations of many oncogenes, such as MYC, or tumor suppressor genes are involved in the metabolic switch of cancer cells to aerobic glycolysis. Myc was the first oncogenic transcription factor reported to regulate microRNAs (miRNAs), which are non-coding RNAs of ~22-nucleotides that act as post-transcriptional regulators of gene expression. Hundreds of miRNAs have been identified in the human genome thus far that are estimated to regulate about 30% of human genes involved in diverse processes including development, cell differentiation, cell proliferation, apoptosis, and metabolism. In this chapter, I will review the characteristics of cancer metabolism and its molecular basis, with an emphasis on the interplay of miRNAs and oncogenes/tumor suppressors in the field. It is hoped that understanding of molecular basis of cancer metabolism, including the involvement of miRNAs, will provide new and powerful strategies to target this deadly disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Baas AF, Kuipers J, van der Wel NN, et al. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell. 2004;116:457–66.

    Article  CAS  PubMed  Google Scholar 

  • Bensaad K, Tsuruta A, Selak MA, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006;126:107–20.

    Article  CAS  PubMed  Google Scholar 

  • Boudeau J, Baas AF, Deak M, et al. MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J. 2003;22:5102–14.

    Article  CAS  PubMed  Google Scholar 

  • Chan SY, Zhang YY, Hemann C, et al. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 2009;10:273–84.

    Article  CAS  PubMed  Google Scholar 

  • Chang TC, Mendell JT. MicroRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet. 2009;8:215–39.

    Article  Google Scholar 

  • Chang TC, Yu D, Lee YS, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2008;40:43–50.

    Article  CAS  PubMed  Google Scholar 

  • Cho WC. MicroRNAs in cancer – from research to therapy. Biochim Biophys Acta. 2010;1805:209–17.

    CAS  PubMed  Google Scholar 

  • Cole MD. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361–84.

    Article  CAS  PubMed  Google Scholar 

  • Cory S, Harris AW, Langdon WY, et al. The myc oncogene and lymphoid neoplasia: from translocations to transgenic mice. Hamatol Bluttransfus. 1987;31:248–51.

    CAS  Google Scholar 

  • Crosby ME, Kulshreshtha R, Ivan M, et al. MicroRNA Regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 2009;69:1221–9.

    Article  CAS  PubMed  Google Scholar 

  • Dang CV, Kim JW, Gao P, et al. The interplay between MYC and HIF in cancer. Nat Rev Cancer. 2008;8:51–6.

    Article  CAS  PubMed  Google Scholar 

  • Easton JB, Houghton PJ. mTOR and cancer therapy. Oncogene. 2006;25:6436–46.

    Article  CAS  PubMed  Google Scholar 

  • Fasanaro P, D’Alessandra Y, Di Stefano V, et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem. 2008;283:15878–83.

    Article  CAS  PubMed  Google Scholar 

  • Favaro E, Ramachandran A, McCormick R, et al. MicroRNA-210 regulates mitochondrial free radical response to hypoxia and Krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS One. 2010;5:e10345.

    Google Scholar 

  • Fukuda R, Zhang H, Jim JW, et al. HIF-1 regulates cytochrome oxidase subunit composition to optimize efficiency of respiration in hypoxic cells. Cell. 2007;129:111–22.

    Article  CAS  PubMed  Google Scholar 

  • Gao P, Tchernyshyov I, Chang TC, et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 2009;458:762–5.

    Article  CAS  PubMed  Google Scholar 

  • Giannakakis A, Sandaltzopoulos R, Greshock J, et al. MiR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther. 2008;7:255–64.

    Article  CAS  PubMed  Google Scholar 

  • Godlewski J, Nowicki MO, Bronisz A, et al. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell. 2010;37:620–32.

    Article  CAS  PubMed  Google Scholar 

  • Hawley SA, Boudeau J, Reid JL, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol. 2003;2:28.

    Google Scholar 

  • Hermeking H. p53 enters the MicroRNA world. Cancer Cell. 2007;12:414–8.

    Article  CAS  PubMed  Google Scholar 

  • Inoki K, Li Y, Zhu T, et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4:648–57.

    Article  CAS  PubMed  Google Scholar 

  • Jamerson MH, Johnson MD, Dickson RB. Of mice and Myc: c-Myc and mammary tumorigenesis. J Mammary Gland Biol Neoplasia. 2004;9:27–37.

    Article  PubMed  Google Scholar 

  • Kaelin WG Jr.. ROS: really involved in oxygen sensing. Cell Metab. 2005;1:357–8.

    Article  CAS  PubMed  Google Scholar 

  • Kim JW, Dang CV. Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res. 2006;66:8927–30.

    Article  CAS  PubMed  Google Scholar 

  • Kim JW, Mori S, Nevins JR. Myc-induced microRNAs integrate Myc-mediated cell proliferation and cell fate. Cancer Res. 2010;70:4820–8.

    Article  CAS  PubMed  Google Scholar 

  • Kim JW, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–85.

    Article  PubMed  Google Scholar 

  • Kim JW, Zeller KI, Wang Y, et al. Evaluation of Myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Mol Cell Biol. 2004;24:5923–36.

    Article  CAS  PubMed  Google Scholar 

  • Kulshreshtha R, Ferracin M, Wojcik S, et al. A microRNA signature of hypoxia. Mol Cell Biol. 2007;27:1859–67.

    Article  CAS  PubMed  Google Scholar 

  • Langdon WY, Harris AW, Cory S, et al. The c-myc oncogene perturbs B lymphocyte development in E-mu-myc transgenic mice. Cell. 1986;47:11–18.

    Article  CAS  PubMed  Google Scholar 

  • Lau LF, Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci USA. 1987;84:1182–6.

    Article  CAS  PubMed  Google Scholar 

  • Leder A, Pattengale PK, Kuo A, et al. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986;45:485–95.

    Article  CAS  PubMed  Google Scholar 

  • Matoba S, Kang JG, Patino WD, et al. P53 regulates mitochondrial respiration. Science. 2006;312:1650–3.

    Article  CAS  PubMed  Google Scholar 

  • O’Donnell KA, Wentzel EA, Zeller KI, et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839–43.

    Article  PubMed  Google Scholar 

  • Olive V, Bennett MJ, Walker JC, et al. MiR-19 is a key oncogenic component of miR-17-92. Genes Dev. 2009;23:2839–49.

    Article  CAS  PubMed  Google Scholar 

  • Oren M. Decision making by p53: life, death and cancer. Cell Death Differ. 2003;10:431–42.

    Article  CAS  PubMed  Google Scholar 

  • Papandreou I, Cairns RA, Fontana L, et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006;3:187–97.

    Article  CAS  PubMed  Google Scholar 

  • Park SY, Lee JH, Ha M, et al. MiR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol. 2009;16:23–9.

    Article  CAS  PubMed  Google Scholar 

  • Phang JM, Liu W, Zabirnyk O. Proline metabolism and microenvironmental stress. Annu Rev Nutr. 2010;30:441–63.

    Article  CAS  PubMed  Google Scholar 

  • Rana TM. Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol. 2009;8:23–36.

    Article  Google Scholar 

  • Sachdeva M, Zhu S, Wu F, et al. P53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA. 2009;106:3207–12.

    Article  CAS  PubMed  Google Scholar 

  • Sanders MJ, Ali ZS, Hegarty BD, et al. Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem. 2007;282:32539–48.

    Article  CAS  PubMed  Google Scholar 

  • Semenza GL. Targeting HIF-1 for cancer therapy. Nature Rev Cancer. 2003;3:721–32.

    Article  CAS  Google Scholar 

  • Semenza GL, Roth PH, Fang HM, et al. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994;269:23757–63.

    CAS  PubMed  Google Scholar 

  • Sheiness D, Bishop JM. DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol. 1979;31:514–21.

    CAS  PubMed  Google Scholar 

  • Shim H, Dolde C, Lewis BC, et al. C-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA. 1997;94:6658–63.

    Article  CAS  PubMed  Google Scholar 

  • Shin S, Cha HJ, Lee EM, et al. MicroRNAs are significantly influenced by p53 and radiation in HCT116 human colon carcinoma. Int J Oncol. 2009;34:1645–52.

    CAS  PubMed  Google Scholar 

  • Suzuki HI, Yamagata K, Sugimoto K, et al. Modulation of microRNA processing by p53. Nature. 2009;460:529–33.

    Article  CAS  PubMed  Google Scholar 

  • Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effct: the metabolic requirements of cell proliferation. Science. 2009;324:1029–33.

    Article  CAS  PubMed  Google Scholar 

  • Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10.

    Article  CAS  PubMed  Google Scholar 

  • Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol. 2007;8:275–83.

    Article  CAS  PubMed  Google Scholar 

  • Warburg O. On respiratory impairment in cancer cells. Science. 1956;124:269–70.

    CAS  PubMed  Google Scholar 

  • Wise DR, DeBerardinis RJ, Mancuso A, et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA. 2008;105:18782–7.

    Article  CAS  PubMed  Google Scholar 

  • Xiao C, Srinivasan L, Calado DP, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008;9:405–14.

    Article  CAS  PubMed  Google Scholar 

  • Yuneva M. Finding an “Achilles’ heel” of cancer: the role of glucose and glutamine metabolism in the survival of transformed cells. Cell Cycle. 2008;7:2083–9.

    Article  CAS  PubMed  Google Scholar 

  • Zeller KI, Zhao X, Lee CW, et al. Global mapping of c-Myc binding sites and target gene networks in human B cells. Proc Natl Acad Sci USA. 2006;103:17834–9.

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Bosch-Marce M, Shimoda LA, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 2008;283:10892–903.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

I thank Dr. Chi Dang for his critical suggestions. Our original work is supported by NIH, Leukemia and Lymphoma Society, and Maryland Stem Cell Research Foundation grants.

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ping Gao

  2. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, PR China

    Ping Gao

Authors
  1. Ping Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ping Gao .

Editor information

Editors and Affiliations

  1. , Department of Clinical Oncology, Queen Elizabeth Hospital, Gascoigne Road 30, Hong Kong SAR, China, People's Republic

    William C.S. Cho

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Netherlands

About this chapter

Cite this chapter

Gao, P. (2011). MicroRNAs and Cancer Metabolism. In: Cho, W. (eds) MicroRNAs in Cancer Translational Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0298-1_20

Download citation

Publish with us

Policies and ethics

Search

Navigation