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

被引：124

作者：

Gregersen, Lea H. ^{[1
,2
,3
,4
]}

Jacobsen, Anders ^{[3
,5
]}

Frankel, Lisa B. ^{[1
,2
]}

Wen, Jiayu ^{[3
]}

Krogh, Anders ^{[1
,2
,3
]}

Lund, Anders H. ^{[1
,2
]}

机构：

[1] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen N, Denmark

[2] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen N, Denmark

[3] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen N, Denmark

[4] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, D-13125 Berlin, Germany

[5] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10021 USA

来源：

BMC CANCER | 2012年 / 12卷

关键词：

miR-143; Colon cancer; Hexokinase; 2; Glycolysis; GENE SET ENRICHMENT; SEMAPHORIN; 5A; EXPRESSION; AND-145; MIR-143; TARGET; SIGNATURES; INVASION; PATHWAY; MIR-21;

D O I：

10.1186/1471-2407-12-232

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：10

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