In contrast, silencing of COX4 in MTC-derived TT cells was associated with downregulation of genes controlling cell cycle (MKi67, MCM2, E2F4, SKP2 and WEE1), and up-regulation of genes related to DNA damage (DDIT3), senescence (TBX2), and hypoxia (HMOX1 and CA9). Here, E2F4 is linked to medullary thyroid gland carcinoma.