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Logo of bmccancBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Cancer
 
BMC Cancer. 2012; 12: 232.
Published online 2012 June 12. doi:  10.1186/1471-2407-12-232
PMCID: PMC3480834
Copyright ©2012 Gregersen et al.; licensee BioMed Central Ltd.
MicroRNA-143 down-regulates Hexokinase 2 in colon cancer cells
Lea H Gregersen,1,2,3 Anders Jacobsen,2,4 Lisa B Frankel,1 Jiayu Wen,2 Anders Krogh,1,2 and Anders H Lundcorresponding author1
1Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200, Copenhagen N, Denmark
2The Bioinformatics Centre, Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark
3Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany
4Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
corresponding authorCorresponding author.
Lea H Gregersen: lea.gregersen/at/mdc-berlin.de; Anders Jacobsen: andersmbj/at/gmail.com; Lisa B Frankel: lisa.frankel/at/bric.ku.dk; Jiayu Wen: Jeanwen/at/binf.ku.dk; Anders Krogh: krogh/at/binf.ku.dk; Anders H Lund: anders.lund/at/bric.ku.dk
Received October 25, 2011; Accepted May 15, 2012.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract
Background
MicroRNAs (miRNAs) are well recognized as gene regulators and have been implicated in the regulation of development as well as human diseases. miR-143 is located at a fragile site on chromosome 5 frequently deleted in cancer, and has been reported to be down-regulated in several cancers including colon cancer.
Methods
To gain insight into the role of miR-143 in colon cancer, we used a microarray-based approach in combination with seed site enrichment analysis to identify miR-143 targets.
Results
As expected, transcripts down-regulated upon miR-143 overexpression had a significant enrichment of miR-143 seed sites in their 3'UTRs. Here we report the identification of Hexokinase 2 (HK2) as a direct target of miR-143. We show that re-introduction of miR-143 in the colon cancer cell line DLD-1 results in a decreased lactate secretion.
Conclusion
We have identified and validated HK2 as a miR-143 target. Furthermore, our results indicate that miR-143 mediated down-regulation of HK2 affects glucose metabolism in colon cancer cells. We hypothesize that loss of miR-143-mediated repression of HK2 can promote glucose metabolism in cancer cells, contributing to the shift towards aerobic glycolysis observed in many tumors.
Keywords: miR-143, Colon cancer, Hexokinase 2, Glycolysis
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