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

BMC Cancer. 2012 Jun 12;12:232. doi: 10.1186/1471-2407-12-232.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Hexokinase / genetics*
  • Hexokinase / metabolism
  • Humans
  • MicroRNAs / genetics*
  • RNA Interference
  • Signal Transduction

Substances

  • MIRN143 microRNA, human
  • MicroRNAs
  • Hexokinase