关键词: microRNA, p53基因, 基因调控

Abstract: As a key tumor suppressor, p53 plays an important role in the suppression of tumorgenesis, which functions as a transcription factor, controlling the expression of a number of target genes. Oscillations of p53 expression were observed after DNA damage. Some models were proposed to explain the mechanism for p53 oscillations. However, many of these models suggest that the time delay between p53 and Mdm2 is the key factor triggering the oscillations. This paper proposes a new model based on chemical kinetics in which the transcriptional and translational process are considered separately and sufficient conditions for p53 oscillations are given by application of the Hopf bifurcation theory. Numerical simulations indicate that our model is more robust to parameter variations compared with the time delay models, thus giving a better explanation to the mechanism for p53 oscillations. Recently, microRNAs regulated by p53 were identified by several experimental studies. These studies highlight the microRNAs miR-34 as direct, conserved p53 target genes and suggest that miR-34 as central mediators of p53 target genes regulates their expression at post-transcriptional level. The regulation effects of miR-34 in our framework model are briefly investigated. Numerical evidences are given to show that microRNAs have a refined regulation of p53 target genes.

Key words: gene regulation, microRNA, p53 gene