In vitro studies performed by Hamada and co-workers observed that miR-221 decreased the expression of Forkhead box O3a (Foxo3a) and apoptotic peptidase activating factor 1 (Apaf-1), both of which are known to be involved in apoptosis in PC12 cells (derived from a pheochromocytoma- rat adrenal medulla). Here, APAF1 is linked to hereditary pheochromocytoma-paraganglioma.