Integrating Metabolomics and Transcriptomics for Probing Se Anticancer Mechanisms

Abstract

Transcriptomics provides the tool for deciphering gene expression networks, and proteomics links these networks to protein products. The third crucial partner is metabolomics, which defines the metabolic network(s) linked to gene expression. NMR and mass spectrometry enable the broad screen analysis of the metabolome and its transformation pathways, transcending classical targeted metabolic studies. These tools were combined to investigate the anticancer mechanisms of different selenium forms in human lung cancer cells. Using 2-D NMR and tandem-MS, we mapped perturbations of ¹³C labeling patterns in numerous metabolites induced by selenite and selenomethionine. This information was used to interpret selenite-induced changes in gene expression networks. Linking metabolic dysfunctions to altered gene expression profiles provided new insights into the regulatory network underlying the metabolic dysfunctions, enabled the assembly of discrete gene expression events into functional pathways, and revealed protein targets for proteomic analysis.

Key Words :

• Two-dimensional NMR
• GC-tandem MS
• FT-MS
• ¹³C isotopomer profiling
• Selenite
• Selenomethionine
• Lung adenocarcinoma A549 cells

Notes

*Presented at the Seventh International Symposium on Biological Reactive Intermediates, Tucson, Arizona, January 4–7, 2006.