Abstract
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.
Highlights
MicroRNAs 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
We show, that reintroduction of miR-143 leads to a decrease in lactate secretion, indicating that miR-143-mediated downregulation of hexokinase 2 (HK2) impairs the rate of glycolysis
We chose to focus our further studies on the human colon cancer cell line DLD-1 since miR-143 expression was virtually absent from this cell line and mimics the situation reported in colon cancer tumors
Summary
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. MicroRNAs (miRNAs) represent an abundant group of small non-coding RNAs that repress translation and promote degradation of their mRNA targets through binding to partially complementary regions in the 3'UTR [1,2,3]. A large number of miRNAs are encoded by genes located in regions frequently exposed to changes in cancer cells [6] and alterations of miRNA expression levels have been associated with various types of cancer [7]. By downregulation of protein-encoding genes either promoting or inhibiting cell proliferation, several miRNAs have been shown to function as tumorsuppressors and oncogenes [5,8,9,10,11]
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