MiRNA regulation model with two negative feedback loops

S.G. Nikolov, M.I. Nenov

Резюме: Various studies documented that small non-coding segments of RNA (called microRNAs (miRNAs)) are involved in the transcriptional and post-transcriptional genetic regulation of tumor oncogenes due to mutations (or deletions of tumor suppressor genes). They are also known to play an important role in regulation of drug sensitivity and/or resistance to chemotherapeutic agents. Therefore, mathematical modeling of miRNA regulations can help us understand in details the mechanisms of these processes.
In the present paper we develop a time delay model with two redundant negative feedback loops one of them regulated via miRNA. The model resulted in three DDEs with three discrete time delays. Since this system is a case study of the superimposition of oscillations induced by redundant delayed negative feedback loops, general conclusions about design principles and role of time delays in the stability of gene circuits can be suggested. The basic view that time delays are a key factor in the dynamic behavior of our model was confirmed by analytical calculations (where the Hopf bifurcation theorem was employed) and numerical simulations. In more details, we derived that time delays have a destabilizing role as from biological point of view, the loss of stability might be related to emergence of new configurations in the regulatory gene circuit that could lead the system to a pathological state.

Series on Biomechanics, Vol.30, No.3 (2016), 5-12

Ключови думи: Mathematical model; MiRNA regulation; Negative feedback loop; Time delay

Дата на публикуване: 2017-02-03