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Инд. авторы: Senotrusova S.D., Voropaeva O.F.
Заглавие: Mathematical Modeling of a Positive Connection in the p53-microRNA Tumor Marker System
Библ. ссылка: Senotrusova S.D., Voropaeva O.F. Mathematical Modeling of a Positive Connection in the p53-microRNA Tumor Marker System // Numerical Analysis and Applications. - 2019. - Vol.12. - Iss. 3. - P.270-283. - ISSN 1995-4239. - EISSN 1995-4247.
Внешние системы: DOI: 10.1134/S1995423919030066; РИНЦ: 41694685; SCOPUS: 2-s2.0-85071937229; WoS: 000485274000006;
Реферат: eng: A hierarchy of minimal mathematical models of the dynamics of the p53-Mdm2- microRNA system has been developed. The models are based on differential equations with a time delay, describing complex interaction mechanisms in the signal system of the p53 protein. We consider two types of interaction of p53 with microRNAs: a positive direct connection and a positive feedback. The feedback of microRNA-p53 is due to a negative effect of the microRNA on the Mdm2 protein, which is a negative regulator of p53. To approximate the direct positive effect of p53 on the microRNAs, a linear function or a representation of the Goldbeter-Koshland type is used. A comparison of numerical solutions with medical and biological data of a number of specific p53-dependent microRNAs is made, which proves that the models and the numerical analysis results are adequate. Special attention is given to analysis of a positive feedback of p53 and microRNAs. The minimal models allow us to consider the most general regularities of the p53-dependent microRNAs. Within the framework of these mathematical models it is shown that it is possible to neglect the Mdm2-miRNA connection for at least some of the most studied microRNAs associated with a direct positive connection with p53. However, those of the microRNAs that are an important negative regulator of Mdm2, can have the most significant impact on the entire p53-Mdm2-microRNA system. Conditions are obtained to manifest the regulatory function of microRNAs with respect to p53. The results of the numerical experiments indicate that such microRNAs can be used as a factor of an anticancer therapy.
Ключевые слова: KEY; NETWORK; APOPTOSIS; MICRORNAS; P53; cancer; miR-145; miR-34; positive feedback; microRNA; Mdm2; p53; tumor marker; delay equation; mathematical modeling;
Издано: 2019
Физ. характеристика: с.270-283
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