Abstract

Abstract microRNAs (miRNAs) are small RNAs average only 22 nucleotides long. miRNA signatures have been associated with histopathological and clinical features, suggesting a potential role of these molecules as prognostic and predictive markers. In this study, we generated a cisplatin resistance cell line. We profiled miRNA and mRNA expression in this cisplatin resistant cells and its parental cells using Exqon miRNA array platform and Affymetrix 1.0 ST array respectively. In order to identify functional regulatory gene-miRNA pairs in cisplatin resistance, we constructed a deregulated miRNA-gene network by incorporating miRNA-target genes information from TargetScan. The resulting miRNA-gene deregulation network consists of 72 genes and 27 miRNAs. 30 genes were up regulated and 42 were down regulated. Of the miRNAs, 26 were down regulated and 1 was up regulated. The network was further refined by retaining the negative correlated pairs considering that miRNAs predominantly decrease their target mRNA levels. We found several members of has-let-7 family were present in the network. IGF pathway gene, IGF2BP1, was also an important node. In our previous work, this pathway was identified as a promising target for cisplatin resistance treatment. Our results show that the has-let-7 miRNA family and IGF pathway genes may play important roles in cisplatin resistance. Exploration of the deregulation network can potentially provide more insights to the identification of candidate targets. Our approach also demonstrates the value of systems biology in the analysis of genomic data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 170. doi:10.1158/1538-7445.AM2011-170

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