Abstract
Abstract Given the fundamental role of microRNA (miRNA) expression in physiological, developmental and pathological processes, we hypothesize that genes involved in miRNA biogenesis and processing are also important in human complex traits. We identified fifty two such genes and evaluated their expression for their roles in cellular growth and sensitivity to various chemotherapeutic agents in a set of 120 International HapMap cell lines. Gene expression data were obtained through microarray-based gene expression profiling (Affymetrix GeneChip® Human Exon 1.0 ST array) and high-throughput sequencing of the transcriptome (RNA-Seq); data on sensitivity to chemotherapeutic drugs carboplatin, cisplatin, daunorubicin and etoposide were queried using a publicly available pharmacogenomics resource we developed (www.PACdb.org). We found 14 (27%) and 24 (47%) of these miRNA processing gene expression correlated with cellular growth rate and at least one of the 4 chemotherapeutic sensitivities, respectively. Regression analysis for expression between miRNA processing genes and genome-wide miRNAs (quantified using Exiqon miRCURYTM LNA arrays) suggests that the miRNA processing genes affect miRNAs and downstream target genes, leading to complex traits variability. Furthermore, from the results of genome-wide association studies we conducted between genetic variations (in the form of single nucleotide polymorphisms (SNPs) and copy number variations (CNVs)) and miRNA processing genes, we demonstrated that genetic variations that affect the expression of these miRNA processing genes as potential expression quantitative trait loci (eQTLs) also have downstream effects on human complex phenotypes, including cellular growth, sensitivity to chemotherapy and disease susceptibility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1643. doi:1538-7445.AM2012-1643
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