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 p...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.展开更多
基金supported by the National Natural Science Foundation of China under Grant No.11762011.
文摘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.
