Oncoprotein MDM2 is the main E3 ubiquitin ligase of p53 tumor suppressor, and circFoxo3 promotes MDM2-induced p53 ubiquitination and subsequent degradation, resulting in a decrease in p53 expression, and circFoxo3 could prevent MDM2-induced Foxo3 ubiquitination and degradation, resulting in increased Foxo3 protein levels, which in turn induced apoptosis [70,71]. This evidence concerns the gene FOXO3 and neoplasm.