title: Modeling of miRNA and drug action in the EGFR signaling pathway.
abstract: MicroRNAs have gained significant interest due to their widespread occurrence and diverse functions as regulatory molecules, which are essential for cell division, growth, development and apoptosis in eukaryotes. The epidermal growth factor receptor (EGFR) signaling pathway is one of the best investigated cellular signaling pathways regulating important cellular processes and its deregulation is associated with severe diseases, such as cancer. In this study, we introduce a systems biological model of the EGFR signaling pathway integrating validated miRNA-target information according to diverse studies, in order to demonstrate essential roles of miRNA within this pathway. The model consists of 1241 reactions and contains 241 miRNAs. We analyze the impact of 100 specific miRNA inhibitors (anit-miRNAs) on this pathway and propose that the embedded miRNA-network can help to identify new drug targets of the EGFR signaling pathway and thereby support the development of new therapeutic strategies against cancer.
authors.affiliation: Department Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. jianli@molgen.mpg.de
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Vikash
authors.initials: V
authors.lastname: Pandey
authors.forename: Thomas
authors.initials: T
authors.lastname: Kessler
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Christoph
authors.initials: C
authors.lastname: Wierling
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003198:Computer Simulation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D066246:ErbB Receptors