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


CONCLUSIONS
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.
Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, DK-2200, Copenhagen N, Denmark.
Lea H
LH
Gregersen
Anders
A
Jacobsen
Lisa B
LB
Frankel
Jiayu
J
Wen
Anders
A
Krogh
Anders H
AH
Lund
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006593:Hexokinase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D015398:Signal Transduction
C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D006593:Hexokinase