title: High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic 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 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.
authors.affiliation: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Röhr
authors.forename: Martin
authors.initials: M
authors.lastname: Kerick
authors.forename: Axel
authors.initials: A
authors.lastname: Fischer
authors.forename: Alexander
authors.initials: A
authors.lastname: Kühn
authors.forename: Karl
authors.initials: K
authors.lastname: Kashofer
authors.forename: Bernd
authors.initials: B
authors.lastname: Timmermann
authors.forename: Andriani
authors.initials: A
authors.lastname: Daskalaki
authors.forename: Thomas
authors.initials: T
authors.lastname: Meinel
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Drichel
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Börno
authors.forename: Anja
authors.initials: A
authors.lastname: Nowka
authors.forename: Sylvia
authors.initials: S
authors.lastname: Krobitsch
authors.forename: Alice C
authors.initials: AC
authors.lastname: McHardy
authors.forename: Christina
authors.initials: C
authors.lastname: Kratsch
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Andrea
authors.initials: A
authors.lastname: Wunderlich
authors.forename: Christian
authors.initials: C
authors.lastname: Barmeyer
authors.forename: Christian
authors.initials: C
authors.lastname: Viertler
authors.forename: Kurt
authors.initials: K
authors.lastname: Zatloukal
authors.forename: Christoph
authors.initials: C
authors.lastname: Wierling
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Michal R
authors.initials: MR
authors.lastname: Schweiger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger