The impact of transcriptional and translational time delays on the cancer network regulated by MicroRNA‐17‐92

Abstract

In this paper, we have formulated and analyzed a mathematical model with multiple time delays of the genetic regulatory network of the microRNA‐17‐92 (miR‐17‐92) cluster. We have focused on the effect of the associated transcriptional and translational time delays of both positive and negative feedback loops on the miR‐17‐92 regulatory network. To gain better insight, we have explored the role of individual time delay in controlling the transition of the G1/S cell cycle process. We pay particular attention to the concentration of E2F and Myc, which trigger the protein ON and OFF switches. To analyze the situation mathematically, we employ delay‐dependent stability analysis and bifurcation analysis using delay differential equations and a biological study of the time‐delayed random transitions between the ON and OFF states for protein synthesis. Based on our study, we can conclude that the translational time delay can halt the healthy transition of cells in the G1/S cell cycle phase as the small increase in can destroy bistability of the system. Simulations are carried out to numerically show the solution trajectories under the combined effect of delays. Finally, we summarize the simulation results and the impact of delays on the dual behavior of miR‐17‐92 as it can act as an oncogene or as a tumor suppressor gene.