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

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.