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.

肿瘤抑制因子 p53 位于细胞 DNA 损伤反应网络的中心。P53 依赖性细胞命运决定与 p53 动力学密不可分。一类非编码microRNA miR-34具有提高p53含量的功能。一个有趣的问题出现了：miR-34 如何影响 p53 动力学？为了解决这个问题，我们重建了一个包含 miR-34 的 p53 信号转导网络模型。复制p53脉冲的一些实验现象来解释模型的合理性。数值分叉法用于研究 miR-34 对 p53 动力学的影响。我们指出，适当或更高的 miR-34 转录率可以分别通过引起 p53 振荡或高稳态动力学行为来防止 DNA 损伤的细胞增殖。然而，缺乏 miR-34 合成能力会导致 p53 保持在低水平，细胞无法正确应对 DNA 损伤。这些结果非常符合 miR-34 的抗癌作用。我们的工作阐明了 miR-34 如何从调节 p53 动态方面发挥其肿瘤抑制功能。