microRNA and mRNA expression signatures of Myc and E2F1 oncogenic pathways

A80

While the use of gene expression profiles to differentiate various tumor subtypes according to their physiology has become a common practice in cancer biology, efforts to utilize the ensuing data to better understand the biology of cancer have been limited. To this end, we recently generated a series of messenger RNA signatures reflecting deregulated oncogenic pathways. These signatures are capable of predicting pathway status of a given tumor, and potentially to serve as a platform for guided therapeutics in a clinical setting. A critical component of the gene regulatory complexity derives from the microRNAs, small regulatory RNA molecules that have been shown to play important roles in key cellular processes, aberration of which lead to numerous pathologies, including cancer. Given their regulatory capacities, obtaining unique expression profiles of microRNAs in the context of various oncogenic pathways will enrich us of information regarding gene regulation that will not only complement aforementioned mRNA expression oncogenic pathway predictor, but will also set the stage for further investigation on the role of these miRNAs in oncogenesis. Indeed, our studies demonstrate that unique miRNA signatures can be generated that can predict the deregulation of the Myc and E2F1 pathways. We further show that microRNA data can be combined with mRNA microarray expression data, using classification tree models, to generate a signature of Myc pathway activation that integrates the two datasets. Among the miRNAs that contributed to the confirmed signature was miR-20a, one that has been previously reported to be a direct transcriptional target of Myc, further supporting the validity of this approach. Taken together, these results suggest that microRNAs are inherent component of major oncogenic pathways, whose information may further contribute to our understanding of malignant processes.