MiRImpact, a new bioinformatic method using complete microRNA expression profiles to assess their overall influence on the activity of intracellular molecular pathways

MicroRNAs (miRs) are short noncoding RNA molecules that regulate expression of target mRNAs. Many published sources provide information about miRs and their targets. However, bioinformatic tools elucidating higher level impact of the established total miR profiles, are still largely missing.

Recently, we developed a method termed OncoFinder enabling quantification of the activities of intracellular molecular pathways basing on gene expression data. Here we propose a new technique, MiRImpact, which enables to link miR expression data with its estimated outcome on the regulation of molecular pathways, like signaling, metabolic, cytoskeleton rearrangement, and DNA repair pathways. MiRImpact uses OncoFinder rationale for pathway activity calculations, with the major distinctions that (i) it deals with the concentrations of miRs - known regulators of gene products participating in molecular pathways, and (ii) miRs are considered as negative regulators of target molecules, if other is not specified. MiRImpact operates with 2 types of databases: for molecular targets of miRs and for gene products participating in molecular pathways. We applied MiRImpact to compare regulation of human bladder cancer-specific signaling pathways at the levels of mRNA and miR expression. We took 2 most complete alternative databases of experimentally validated miR targets - miRTarBase and DianaTarBase, and an OncoFinder database featuring 2725 gene products and 271 signaling pathways. We showed that the impact of miRs is orthogonal to pathway regulation at the mRNA level, which stresses the importance of studying posttranscriptional regulation of gene expression. We also report characteristic set of miR and mRNA regulation features linked with bladder cancer.

Cell cycle (Georgetown, Tex.). 2016 Mar 03 [Epub]

Alina V Artcibasova, Mikhail B Korzinkin, Maksim I Sorokin, Peter V Shegay, Alex A Zhavoronkov, Nurshat Gaifullin, Boris Y Alekseev, Nikolay V Vorobyev, Denis V Kuzmin, Аndrey D Kaprin, Nikolay M Borisov, Anton A Buzdin

a Pathway Pharmaceuticals , Wan Chai , Hong Kong, Hong Kong SAR., c First Oncology Research and Advisory Center , Moscow , Russia., a Pathway Pharmaceuticals , Wan Chai , Hong Kong, Hong Kong SAR., d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia., b Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia., e Moscow State University, Faculty of Fundamental Medicine , Moscow , Russia., d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia., d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia., f Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry , Moscow , Russia., d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia., g National Research Centre "Kurchatov Institute," Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies , Moscow , Russia., b Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.

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