Self-induced Stochastic Resonance in MicroRNA Regulation of a Cancer Network

The transcription factors (TFs) EF2 and Myc, which participate in the control of cell proliferation and apoptosis and can act as oncogenes or tumor suppressors depending on their levels of expression, are inhibited at the posttranscriptional level by some microRNAs (miRs). The consequences of coupling between these TFs and miRs were investigated by using a mathematical model, which predicted these miRs can play a critical role in regulating the position of the off-on switch in EF2/Myc protein levels and determining the levels of these proteins. In this work, we study the properties of switching behavior induced by stochastic fluctuations. Based on the Kramers escape rate in statistic dynamics, we derive the following conclusion: when the noise increases to reach the threshold, the stochastic resonance will appear, and the E2F/Myc and iniR-17-92 will burst, which may result in the increase of the probability for the system to enter the state of cancer. The average bursting period for the E2F/Myc and miR-17-92 will decrease as the noise intensity increases. These phenomena induced by small noise not only reveal the possible mechanism of the biological processes but also can be used to control cancer progress, e.g. by perturbing small noise.