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Modeling microRNA-Transcription Factor Networks in Cancer

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MicroRNA Cancer Regulation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 774))

Abstract

An increasing number of transcription factors (TFs) and microRNAs (miRNAs) is known to form feedback loops (FBLs) of interactions where a TF positively or negatively regulates the expression of a miRNA, and the miRNA suppresses the translation of the TF messenger RNA. FBLs are potential sources of instability in a gene regulatory network. Positive FBLs can give rise to switching behaviors while negative FBLs can generate periodic oscillations. This chapter presents documented examples of FBLs and their relevance to stem cell renewal and differentiation in gliomas. Feed-forward loops (FFLs) are only discussed briefly because they do not affect network stability unless they are members of cycles. A primer on qualitative network stability analysis is given and then used to demonstrate the network destabilizing role of FBLs. Steps in model formulation and computer simulations are illustrated using the miR-17-92/Myc/E2F network as an example. This example possesses both negative and positive FBLs.

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Abbreviations

CZ:

cancer zone

dTF:

differentiation transcription factor module

FFL:

feed-forward loop

FBL:

feedback loop

PA :

apoptosis factors

PC :

cell cycle factors

qNET:

qualitative network

sTF:

stem cell transcription factor module

TF:

transcription factor

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Author information

Authors and Affiliations

  1. Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Baltazar D. Aguda

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  1. Baltazar D. Aguda
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Correspondence to Baltazar D. Aguda .

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Editors and Affiliations

  1. Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany

    Ulf Schmitz

  2. Dept. of Systems Biology and Bioinformat, Universität Rostock Institut of Computer Science, Rostock, Germany

    Olaf Wolkenhauer

  3. Rostock, Germany

    Julio Vera

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Aguda, B.D. (2013). Modeling microRNA-Transcription Factor Networks in Cancer. In: Schmitz, U., Wolkenhauer, O., Vera, J. (eds) MicroRNA Cancer Regulation. Advances in Experimental Medicine and Biology, vol 774. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5590-1_9

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