Iron metabolism in cells consists mainly of uptake, utilization and efflux processes regulated by many genes and proteins. Genes related to iron metabolism consist mainly of iron uptake genes (TFRC and DMT1), utilization genes (FTH1, FTL, HIF1A, HMOX1, SLC25A37 and SLC25A38) and exporter genes (FLVCR1 and Fpn).
TFRC is a direct downstream target of MYCN and mediates MYCN-induced GPX4-dependent iron death. Sp1 regulates TFRC transcription in cells by binding to the TFRC promoter region.
Potential binding sites for Sp1 within the TFRC promoter region .
Predicted iron-reactive elements
(IREs) in FTH1 .
FTH1 is a major iron storage protein and plays a key role in important signalling pathways triggered by disruptions in iron and ROS levels. Also, downregulation of FTH1 is associated with tumourigenesis in breast and colorectal cancers, suggesting a tumour suppressive role for this key ferritin subunit that maintains iron homeostasis.
Knockdown of Fpn accelerates erastin-induced iron death by increasing the accumulation of iron-dependent lipid ROS, which can be prevented by degradation of Fpn by Hepcidin.