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Issue 11, 2017
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Modelling the propagation of a dynamical signature in gene expression mediated by the transport of extracellular microRNAs

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Abstract

Extracellular microRNAs (miRNAs) carried by exosomes can play a key role in cell-to-cell communication. Deregulation of miRNA expression and exosome secretion have been related to pathological conditions such as cancer. While it is known that circulating miRNAs can alter gene expression in recipient cells, it remains unclear how significant the dynamical impact of these extracellular miRNAs is. To shed light on this issue, we propose a model for the spatio-temporal evolution of the protein expression in a cell tissue altered by abnormal miRNA expression in a donor cell. This results in a nonhomogeneous cellular response in the tissue, which we quantify by studying the range of action of the donor cell on the surrounding cells. Key model parameters that control the range of action are identified. Based on a model for a heterogeneous cell population, we show that the dynamics of gene expression in the tissue is robust to random changes of the parameter values. Furthermore, we study the propagation of gene expression oscillations in a tissue induced by extracellular miRNAs. In the donor cell, the miRNA inhibits its own transcription which can give rise to local oscillations in gene expression. The resulting oscillations of the concentration of extracellular miRNA induce oscillations of the protein concentration in recipient cells. We analyse the nonmonotonic spatial evolution of the oscillation amplitude of the protein concentration in the tissue which may have implications for the propagation of oscillations in biological rhythms such as the circadian clock.

Graphical abstract: Modelling the propagation of a dynamical signature in gene expression mediated by the transport of extracellular microRNAs

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Publication details

The article was received on 19 Aug 2017, accepted on 18 Sep 2017 and first published on 18 Sep 2017


Article type: Paper
DOI: 10.1039/C7MB00509A
Citation: Mol. BioSyst., 2017,13, 2379-2391
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    Modelling the propagation of a dynamical signature in gene expression mediated by the transport of extracellular microRNAs

    A. Grau Ribes, Y. De Decker, C. Gérard and L. Rongy, Mol. BioSyst., 2017, 13, 2379
    DOI: 10.1039/C7MB00509A

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