Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

High-throughput sequencing of matched colorectal normal, tumor and metastasis tissues and proof-of principal bioinformatics modeling of therapeutic consequences of miRNA applications

ABSTRACT: 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 identified miRNA-1 as top candidate differentially expressed in tumor and metastasis. Furthermore, miRNA-1 was de-regulated in 16 additional tumor entities underscoring its central role in tumor pathogenesis. Functional analyses showed an additive effect of miRNA-1 with camptothecin treatment. We used a systems-biology simulation of cellular cancer models implemented in PyBios to investigate miRNA-1 function 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. Examination of miRNA expression values by Illumina sequencing of matched benign, tumor and metastasis tissues of 8 colorectal cancer patients. For 4 of these patients all tissues have been resequenced to obtain mRNA expression values.

ORGANISM(S): Homo sapiens

SUBMITTER: Michal Schweiger

PROVIDER: E-GEOD-46622 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic applications.

Röhr Christina C Kerick Martin M Fischer Axel A Kühn Alexander A Kashofer Karl K Timmermann Bernd B Daskalaki Andriani A Meinel Thomas T Drichel Dmitriy D Börno Stefan T ST Nowka Anja A Krobitsch Sylvia S McHardy Alice C AC Kratsch Christina C Becker Tim T Wunderlich Andrea A Barmeyer Christian C Viertler Christian C Zatloukal Kurt K Wierling Christoph C Lehrach Hans H Schweiger Michal R MR

PloS one 20130702 7

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 ...[more]

PMID: 23874421

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Dataset Information

High-throughput sequencing of matched colorectal normal, tumor and metastasis tissues and proof-of principal bioinformatics modeling of therapeutic consequences of miRNA applications

Publications

High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic applications.

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