FOXO3 and neoplasm: Furthermore, its downstream target, forkhead box O3a (FOXO3A), a well-established tumor suppressor, was activated, along with increases in FOXO3A target genes (cell cycle inhibitor proteins p21 and p27 as well as pro-apoptotic protein p53 upregulated modulator of apoptosis (PUMA) (Figure 6F and Supplementary Figure 6D).