A model-based strategy to investigate the role of microRNA regulation in cancer signalling networks

Abstract

In this paper we present and discuss a model-based approach to link miRNA translational control with cell signalling networks. MicroRNAs are small regulatory RNAs that are able to regulate the activity and the stability of specific messenger RNA and have been implicated in tumour progression due to their ability to translationally regulate critical oncogenes and tumour suppressors. In our approach, data on protein-protein interactions and miRNA regulation, obtained from bioinformatics databases, are integrated with quantitative experimental data using mathematical modelling. Predictive computational simulations and qualitative (bifurcation) analyses of those mathematical models are employed to further support the investigation of such multifactorial networks in the context of cancer progression. We illustrate our approach with the C-Myc/E2F signalling network, involved in the progression of several tumour subtypes, including colorectal cancer.

Computational analysis of target hub gene repression regulated by multiple and cooperative miRNAs

“…The approach here discussed extends and improves our preliminary idea of integrating algorithms for target prediction and databases to develop more comprehensive computational models of miRNA regulatory networks (50). Given the existence of up to 834 target hubs in H omo sapiens (3) , the approach proposed here can be used as a template for other miRNA target hub networks.…”

Modelling and Analysis of miRNA Regulation

“…Recently, an additional level of regulation in protein expression has been introduced following the identification of short non-protein-coding RNAs [22]. MicroRNAs (miRNAs) are small regulatory RNAs with length of 18-25 nucleotides (typically ≈ 22nt size in human), which function is to regulate the activity and stability of specific messenger RNA targets.…”

“…Bifurcation theory studies persistence and exchange of qualitative properties of dynamical systems under continuous perturbations. From the point of view of the dynamic systems theory, the Hopf bifurcation theorem [22] together with other elements of the bifurcation theory are basic analytical tools to investigate pathological conditions in biological systems.…”

A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

“…The systems biology approach, combining data-driven modeling and model-driven experiments, provides a systematic and comprehensive perspective on the regulatory roles of miRNAs in gene regulatory networks [3–5]. To investigate a gene regulatory network, an iterative process of four steps is needed.…”