title: Altered Micro-RNA Degradation Promotes Tumor Heterogeneity: A Result from Boolean Network Modeling.
abstract: Cancer heterogeneity may reflect differential dynamical outcomes of the regulatory network encompassing biomolecules at both transcriptional and post-transcriptional levels. In other words, differential gene-expression profiles may correspond to different stable steady states of a mathematical model for simulation of biomolecular networks. To test this hypothesis, we simplified a regulatory network that is important for soft-tissue sarcoma metastasis and heterogeneity, comprising of transcription factors, micro-RNAs, and signaling components of the NOTCH pathway. We then used a Boolean network model to simulate the dynamics of this network, and particularly investigated the consequences of differential miRNA degradation modes. We found that efficient miRNA degradation is crucial for sustaining a homogenous and healthy phenotype, while defective miRNA degradation may lead to multiple stable steady states and ultimately to carcinogenesis and heterogeneity.
authors: Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, P.R. China.
authors: Yunyi
authors: Y
authors: Wu
authors: Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School, Houston, TX, U.S.A.
authors: Gerhard R F
authors: GR
authors: Krueger
authors: Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, P.R. China wanggy@sustc.edu.cn.
authors: Guanyu
authors: G
authors: Wang
mesh_terms: D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008962:Models, Theoretical; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs
keywords: Tumor heterogeneity; micro-RNA; network modeling