Exploring the influence of microRNA miR-34 on p53 dynamics: a numerical study*

Abstract

Abstract The tumor suppressor p53 is at the hub of the cellular DNA damage response network. P53-dependent cell fate decision is inseparable from p53 dynamics. A type of non-coding microRNA miR-34 has the function of enhancing p53 content. An intriguing question arises: How does miR-34 affect p53 kinetics? To address this question, we reconstruct a p53 signal transduction network model containing miR-34. Some experimental phenomena of p53 pulses are reproduced to explain the rationality of the model. The method of numerical bifurcation is used to investigate the effect of miR-34 on p53 kinetics. We point out that appropriate or higher miR-34 transcription rates can prevent DNA-damaged cell proliferation by causing p53 oscillation or high steady-state kinetic behavior, respectively. However, the lack of miR-34 synthesis ability will induce p53 to remain at a low level, and cells cannot respond correctly to DNA damage. These results are well in line with the anti-cancer role of miR-34. Our work sheds light on how miR-34 carries out its tumor-suppressive function from tuning p53 dynamic aspect.