Nikolov Svetoslav, Vera Julio, Schmitz Ulf, Wolkenhauer Olaf
Institute of Mechanics, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 4, 1113, Sofia, Bulgaria,
Theory Biosci. 2011 Mar;130(1):55-69. doi: 10.1007/s12064-010-0109-5. Epub 2010 Aug 31.
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.
在本文中，我们提出并讨论了一种基于模型的方法，用于将微小RNA（miRNA）的翻译控制与细胞信号网络联系起来。微小RNA是一类小的调节性RNA，能够调节特定信使RNA的活性和稳定性，并且由于其能够对关键癌基因和肿瘤抑制因子进行翻译调控，因而与肿瘤进展有关。在我们的方法中，从生物信息学数据库获得的蛋白质-蛋白质相互作用和miRNA调控数据，通过数学建模与定量实验数据整合在一起。利用这些数学模型的预测性计算模拟和定性（分岔）分析，进一步支持在癌症进展背景下对这种多因素网络的研究。我们以参与包括结直肠癌在内的几种肿瘤亚型进展的C-Myc/E2F信号网络为例来说明我们的方法。
