Journal Article

High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal, Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications

Röhr, Christina, Fischer, Axel, Wierling, Christoph, Nowka, Anja, Kratsch, Christina, Krobitsch, Sylvia, Wunderlich, Andrea, McHardy, Alice C., Kerick, Martin, Schweiger, Michal R., Lehrach, Hans, Timmermann, Bernd, Barmeyer, Christian, Kühn, Alexander, Zatloukal, Kurt, Becker, Tim, Drichel, Dmitriy, Börno, Stefan T., Viertler, Christian, Daskalaki, Andriani, Kashofer, Karl, Meinel, Thomas

2013

Overview

MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Aged, 80 and over / Apoptosis / Binding sites / Bioinformatics / Biology / Cancer / Cell cycle / Cell Line / Chemotherapy / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - genetics / Colorectal Neoplasms - metabolism / Computational Biology - methods / Computer simulation / Development and progression / Diagnostic software / Diagnostic systems / Dihydrofolate reductase / DNA sequencing / Down-Regulation / Drugs / Female / Gene expression / Gene Regulatory Networks - genetics / Gene sequencing / Genes, Tumor Suppressor / Genetic aspects / Genomes / Genomics / Health aspects / High-Throughput Nucleotide Sequencing - methods / Humans / Immunotherapy / Informatics / Laboratories / Male / Medical treatment / Medicine / Metastases / Metastasis / MicroRNA / MicroRNAs / MicroRNAs - genetics / Middle Aged / miRNA / Modelling / Nucleotide sequencing / Pathology / Patients / Pharmacy / Physiological aspects / Physiology / Ribonucleic acid / RNA / RNA, Messenger - genetics / Therapeutic applications / Tissues / Warburg, Otto