title: MicroRNAs modulate the dynamics of the NF-κB signaling pathway.
abstract: BACKGROUND
  NF-κB, a major transcription factor involved in mammalian inflammatory signaling, is primarily involved in regulation of response to inflammatory cytokines and pathogens. Its levels are tightly regulated since uncontrolled inflammatory response can cause serious diseases. Mathematical models have been useful in revealing the underlying mechanisms, the dynamics, and other aspects of regulation in NF-κB signaling. The recognition that miRNAs are important regulators of gene expression, and that a number of miRNAs target different components of the NF-κB network, motivate the incorporation of miRNA regulated steps in existing mathematical models to help understand the quantitative aspects of miRNA mediated regulation.
  
  
  RESULTS
  In this study, two separate scenarios of miRNA regulation within an existing model are considered. In the first, miRNAs target adaptor proteins involved in the synthesis of IKK that serves as the NF-κB activator. In the second, miRNAs target different isoforms of IκB that act as NF-κB inhibitors. Simulations are carried out under two different conditions: when all three isoforms of IκB are present (wild type), and when only one isoform (IκBα) is present (knockout type). In both scenarios, oscillations in the NF-κB levels are observed and are found to be dependent on the levels of miRNAs.
  
  
  CONCLUSIONS
  Computational modeling can provide fresh insights into intricate regulatory processes. The introduction of miRNAs affects the dynamics of the NF-κB signaling pathway in a manner that depends on the role of the target. This "fine-tuning" property of miRNAs helps to keep the system in check and prevents it from becoming uncontrolled. The results are consistent with earlier experimental findings.
authors: School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Candida
authors: C
authors: Vaz
authors: Arvind Singh
authors: AS
authors: Mer
authors: Alok
authors: A
authors: Bhattacharya
authors: Ramakrishna
authors: R
authors: Ramaswamy
mesh_terms: D003198:Computer Simulation; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020672:I-kappa B Proteins; D035683:MicroRNAs; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase