Detection of miRNA regulatory effect on triple negative breast cancer transcriptome. (December 2015)

• Record Type: Journal Article
• Authors: Martignetti, Loredana; Tesson, Bruno; Almeida, Anna; Zinovyev, Andrei; Tucker, Gordon; Dubois, Thierry; Barillot, Emmanuel
• Is Part Of: BMC genomics. Volume 16:Number 6(2015)
• Page Start: 1
• Page End: 10
• Publication Date: 2015-12
• Subjects: Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/1471-2164-16-S6-S4
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Identifying key microRNAs (miRNAs) contributing to the genesis and development of a particular disease is a focus of many recent studies. We introduce here a rank-based algorithm to detect miRNA regulatory activity in cancer-derived tissue samples which combines measurements of gene and miRNA expression levels and sequence-based target predictions. The method is designed to detect modest but coordinated changes in the expression of sequence-based predicted target genes. We applied our algorithm to a cohort of 129 tumour and healthy breast tissues and showed its effectiveness in identifying functional miRNAs possibly involved in the disease. These observations have been validated using an independent publicly available breast cancer dataset from The Cancer Genome Atlas. We focused on the triple negative breast cancer subtype to highlight potentially relevant miRNAs in this tumour subtype. For those miRNAs identified as potential regulators, we characterize the function of affected target genes by enrichment analysis. In the two independent datasets, the affected targets are not necessarily the same, but display similar enriched categories, including breast cancer related processes like cell substrate adherens junction, regulation of cell migration, nuclear pore complex and integrin pathway. The R script implementing our method together with the datasets used in the study can be downloaded here (http://bioinfo-out.curie.fr/projects/targetrunningsum ).