PDCD4 and neoplasm: Mechanisms that are frequently involved in the down-regulation of tumor suppressor genes commonly involve mutational inactivation and deletion [38], however such mechanisms seem not to apply to PDCD4. Several mechanisms of PDCD4 down-regulation were reported, such as hypermethylation of its 5' promoter region in glioma [39], increased proteasomal degradation [40], and silencing by miR-21 [21].