Amit Arora1. 1. Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh, India.
Abstract
BACKGROUND: Gene expression is regulated by trans-acting transcription factors and microRNAs (miRNAs) through interactions with their respective cis-regulatory elements. The effects that drugs induce result from complex interactions in pathways downstream from their primary targets. These interactions, from gene regulatory apparatus and from drug-induced pathways, form a complex, multilayered network. METHODS: Knowing that drugs can perturb miRNA expression profiles, a genomewide analysis of drug-induced intronic miRNA perturbations has been presented here. RESULTS: By comparative analysis of control and drugged data sets from 27 independent gene expression experiments, it was feasible to detect the effect of drugs on miRNA target genes. Signatures of 21 of 28 miRNAs, predicted to be influenced by drug action, were detected. CONCLUSION: This study demonstrates that the action of drugs on mRNA expression can be mediated through the combinatorial effects of miRNAs. In addition, transcription factors, through miRNAs within the introns of their target genes, can exert an indirect effect on the expression of distal mRNAs.
BACKGROUND: Gene expression is regulated by trans-acting transcription factors and microRNAs (miRNAs) through interactions with their respective cis-regulatory elements. The effects that drugs induce result from complex interactions in pathways downstream from their primary targets. These interactions, from gene regulatory apparatus and from drug-induced pathways, form a complex, multilayered network. METHODS: Knowing that drugs can perturb miRNA expression profiles, a genomewide analysis of drug-induced intronic miRNA perturbations has been presented here. RESULTS: By comparative analysis of control and drugged data sets from 27 independent gene expression experiments, it was feasible to detect the effect of drugs on miRNA target genes. Signatures of 21 of 28 miRNAs, predicted to be influenced by drug action, were detected. CONCLUSION: This study demonstrates that the action of drugs on mRNA expression can be mediated through the combinatorial effects of miRNAs. In addition, transcription factors, through miRNAs within the introns of their target genes, can exert an indirect effect on the expression of distal mRNAs.