title: A systems' biology approach to study microRNA-mediated gene regulatory networks.
abstract: MicroRNAs (miRNAs) are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.
authors.affiliation: Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany ; Laboratory of Systems Tumor Immunology, Department of Dermatology, Faculty of Medicine, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Xin
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Dermatology, Venereology and Allergology, University of Leipzig, 04155 Leipzig, Germany.
authors.forename: Animesh
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schmitz
authors.affiliation: Department of Dermatology, Venereology and Allergology, University of Leipzig, 04155 Leipzig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kunz
authors.affiliation: Laboratory of Systems Tumor Immunology, Department of Dermatology, Faculty of Medicine, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Julio
authors.initials: J
authors.lastname: Vera
authors.affiliation: Department of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, Germany ; Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch 7600, South Africa.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wolkenhauer
mesh_terms: D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics
chemical_list: D035683:MicroRNAs; D054462:p21-Activated Kinases