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miR-143 regulates hexokinase 2 expression in cancer cells

Oncogene volume 32, pages 797–802 (2013)Cite this article

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Abstract

Tumor cells activate pathways that facilitate and stimulate glycolysis even in the presence of adequate levels of oxygen in order to satisfy their continuous need of molecules, such as nucleotides, ATP and fatty acids, necessary to support their rapid proliferation. Accordingly, a variety of human tumors are characterized by elevated expression levels of the hexokinase 2 isoform (HK2). Although different molecular mechanisms, including genetic and epigenetic mechanisms, have been suggested to account for the altered expression of HK2 in tumors, the potential role of microRNAs (miRNAs) in the regulation of HK2 expression has not been evaluated. Here, we report that miR-143 inhibits HK2 expression via a conserved miR-143 recognition motif located in the 3′-untranslated region (3′UTR) of HK2 mRNA. We demonstrate that miR143 inhibits HK2 expression both in primary keratinocytes and in head and neck squamous cell carcinoma (HNSCC)-derived cell lines. Importantly, we found that miR-143 inversely correlates with HK2 expression in HNSCC-derived cell lines and in primary tumors. We also report that the miRNA-dependent regulation of hexokinase expression is not limited to HK2 as miR-138 targets HK1 via a specific recognition motif located in its 3′UTR. All these data unveil a new miRNA-dependent mechanism of regulation of hexokinase expression potentially important in the regulation of glucose metabolism of cancer cells.

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Acknowledgements

This work has been supported by the Medical Research Council, UK; grants from ‘Alleanza contro il Cancro’ Grant (ACC12), MIUR/PRIN (20078P7T3K_001)/FIRB (RBIP06LCA9_0023, RBIP06LCA9_0C), AIRC grant no. 5471; 2011-IG11955), Telethon Grant GGPO9133 to GM, MIUR/PRIN 2008MRLSNZ_004, AIRC 5xmille (no. 9979), RF06 c.73, RF08 c.15, RF07 c.57 awarded to GM and EC. Research described in this article was also supported by Ric. Finalizzata 08-GIOV_RIC awarded to AP.

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Authors and Affiliations

  1. Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy

    A Peschiaroli

  2. c/o Department of Experimental Medicine and Biochemical Sciences, IDI-IRCCS Biochemistry Laboratory, University of Rome ″Tor Vergata″, Rome, Italy

    A Peschiaroli, A Formosa & G Melino

  3. Department of Experimental Medicine and Biochemical Sciences, University of Rome ″Tor Vergata″, Rome, Italy

    A Giacobbe, L Bongiorno-Borbone, E Candi & A Finazzi Agrò

  4. The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ, USA

    E K Markert & A J Levine

  5. Department of Enviromental Sciences, University of Tuscia, Viterbo, Italy

    A D'Alessandro & L Zolla

  6. Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK

    G Melino

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  1. A Peschiaroli
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Correspondence to A Peschiaroli or G Melino.

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Peschiaroli, A., Giacobbe, A., Formosa, A. et al. miR-143 regulates hexokinase 2 expression in cancer cells. Oncogene 32, 797–802 (2013). https://doi.org/10.1038/onc.2012.100

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  • DOI: https://doi.org/10.1038/onc.2012.100

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