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

Röhr, C., Kerick, M., Fischer, A., Kuehn, A., Kashofer, K., Timmermann, B., et al. (2013). High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal, Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications. PLoS One, 8(7), e67461-e67461. doi:10.1371/journal.pone.0067461.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-F968-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-CECF-6
Genre: Journal Article

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2013
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2013 Ro¨ hr et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 Creators:
Röhr, C.1, Author              
Kerick, M.1, Author              
Fischer, A., Author
Kuehn, A.2, Author              
Kashofer, K., Author
Timmermann, B.3, Author              
Daskalaki, A.2, Author              
Meinel, T.1, Author
Drichel, D., Author
Börno, S.1, Author              
Nowka, A.4, Author              
Krobitsch, S.4, Author              
McHardy, A. C., Author
Kratsch, C., Author
Becker, T., Author
Wunderlich, A.1, Author              
Barmeyer, C., Author
Viertler, C., Author
Zatloukal, K., Author
Wierling, C.2, Author              
Lehrach, H.5, Author              Schweiger, M.-R.1, Author               more..
Affiliations:
1Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479649              
2Systems Biology (Christoph Wierling), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479656              
3Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
4Neurodegenerative Disorders (Sylvia Krobitsch), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479661              
5Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: human colon-cancer real-time pcr microrna expression down-regulation systems biology genes suppressor cells identification proliferation
 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 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.

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Language(s): eng - English
 Dates: 2013-02-152013-05-172013-07-02
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1371/journal.pone.0067461
ISSN: 1932-6203
 Degree: -

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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 8 (7) Sequence Number: - Start / End Page: e67461 - e67461 Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850