Figure 5.

Effects of cooperative E2F1 repression on chemoresistance. (A) Biochemical reaction network underlying the kinetic model of E2F1-mediated drug resistance. (B) Illustration of a typical model simulation, accounting for the temporal dynamics of E2F1 protein, miR-205-5p, Harakiri protein (Hrk), BCL2 protein and the population of tumour cells (TC) before (shaded area) and after drug administration (white area). (C) Model predicted values of E2F1, miR-205-5p and the ratio between p73 and DNp73 for different combinations of E2F1 and miR-342-3p expression levels, whose corresponding variables FS_E2F1 and FS_miR342 were iteratively modified in the specified intervals. The highlighted and indexed areas correspond to the description in the main text. (D) Predicted tumour cell population size in non-genotoxic drug stimulation conditions (left) and predicted fraction of surviving tumour cells 48 h after genotoxic drug administration (right). The enclosed numbers indicate the transition of tumour growth rate under different biological conditions.