MicroRNA-143 down-regulates Hexokinase 2 in colon cancer cells
1 Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200, Copenhagen N, Denmark
2 The Bioinformatics Centre, Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark
3 Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany
4 Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
BMC Cancer 2012, 12:232 doi:10.1186/1471-2407-12-232Published: 12 June 2012
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.
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.
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.
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.