MicroRNA-143 down-regulates Hexokinase 2 in colon cancer cells

BMC Cancer

Research Article

Lisa B Frankel¹  Anders H Lund¹  Anders Krogh²  Lea H Gregersen³  Jiayu Wen⁴  Anders Jacobsen⁵ 

[1] Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200, Copenhagen N, Denmark;Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200, Copenhagen N, Denmark;The Bioinformatics Centre, Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark;Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200, Copenhagen N, Denmark;The Bioinformatics Centre, Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark;Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, D-13125, Berlin, Germany;The Bioinformatics Centre, Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark;The Bioinformatics Centre, Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark;Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA;

关键词: miR-143;    Colon cancer;    Hexokinase 2;    Glycolysis;   

DOI  :  10.1186/1471-2407-12-232

 received in 2011-10-25, accepted in 2012-05-15,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (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.MethodsTo 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.ResultsAs 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.ConclusionWe 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.

【 授权许可】

Unknown   
© Gregersen et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. 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.