Regulation of P 53 Oscillations by MircoRNA-mediated Positive Feedback Loops

Short Abstract — The tumor suppressor p53 oscillates in response to DNA double-strand breaks. We model a class of ubiquitous post-transcriptional regulators, termed microRNAs, which form positive feedback loops with the p53 regulatory network. Simulations reproduce the oscillation of p53 under DNA damage stimulus. Importantly, model analysis show that specific microRNA abrogation leads to loss of the wild-type phenotype. For evaluation, we perform microRNAperturbation experiments in MCF7 breast cancer cells. Quantitative microscopy analysis confirms that the p53 oscillatory performance is compromised under specific microRNA perturbation. Our results provide evidence of the impact of microRNA-mediated positive feedback loops on the stress-induced p53 oscillations.