MDM2 and cancer: Similarly, Du et al. (2017a) found that the overexpression of circFOXO3 inhibited the interaction between FOXO3 and mouse double minute 2 (MDM2), prevented MDM2 from inducing ubiquitination and degradation of FOXO3, thus increasing the activity of FOXO3 and promoting the expression of PUMA to induce apoptosis of cancer cells (Lin et al., 2020; Figure 1C).