CircFoxo3 was shown to bind CDK2 and p21, which simultaneously facilitated p21-mediated suppression of CDK2 activity and prevented CDK2 from binding cyclin E, arresting cell cycle progression in the G1 phase.16 CircFoxo3 was also shown to bind p53 and MDM2 to form a complex that facilitated MDM2-induced p53 ubiquitination and relieved MDM2-induced Foxo3 ubiquitination, leading to increased PUMA expression and tumor cell apoptosis.17 These studies and others18,19 suggest that circRNAs frequently interact with proteins. This evidence concerns the gene MDM2 and neoplasm.