Hyperactivation of the p53–microRNA signaling pathway: mathematical model of variants of antitumor therapy

O. F. Voropaeva ; P. D. Lisachev ; S. D. Senotrusova ; Yu. I. Shokin

Matematičeskaâ biologiâ i bioinformatika, Tome 14 (2019) no. 1, pp. 355-372.

Résumé

We carried out a numerical simulation of the system p53–inhibitor–microRNA. A minimal mathematical model was used, which describes only the most common features of the functioning of a biological system with a negative feedback p53–inhibitory protein and a positive feedback p53–microRNA. Adequacy of the accepted model and results of the computational analysis is confirmed by agreement with published data of biological experiments. In the frames of the accepted model, possible strategies were descried for the restoration of the p53 and its target microRNAs normal levels for cancer prevention. In addition, possible variants of anticancer therapies were studied, which are associated with the hyperactivation of the regulators of apoptosis p53 and microRNAs. Our results demonstrate potentially high effectiveness of the anticancer therapy targeted on the p53 inhibitor, which is a critical element of the positive feedback chain p53–microRNA.

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