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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 474632, 15 pages
doi:10.1155/2011/474632
MicroRNA Gene Dosage Alterations and Drug Response in Lung Cancer
1British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada
2Research Institute, Nationwide Children's Hospital, Columbus, OH 43205-2664, USA
Received 1 November 2010; Accepted 27 January 2011
Academic Editor: E. Felip
Copyright © 2011 Katey S. S. Enfield et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Chemotherapy resistance is a key contributor to the dismal prognoses for lung cancer patients. While the majority of studies have focused on sequence mutations and expression changes in protein-coding genes, recent reports have suggested that microRNA (miRNA) expression changes also play an influential role in chemotherapy response. However, the role of genetic alterations at miRNA loci in the context of chemotherapy response has yet to be investigated. In this study, we demonstrate the application of an integrative, multidimensional approach in order to identify miRNAs that are associated with chemotherapeutic resistance and sensitivity utilizing publicly available drug response, miRNA loci copy number, miRNA expression, and mRNA expression data from independent resources. By instigating a logical stepwise strategy, we have identified specific miRNAs that are associated with resistance to several chemotherapeutic agents and provide a proof of principle demonstration of how these various databases may be exploited to derive relevant pharmacogenomic results.