Fig. 5.

miR-424/-503 mediated mechanisms in HIF-1α stabilization. In normoxia, HIF-1α is hydroxylated by PHD, using O2 and α-KG. Hydroxylated HIF-1α is recruited to the VCBCR complex in which CUL2 serves as the scaffold. HIF-1α is degraded by the proteasome system. In hypoxia, miR-424(322)/-503 are activated by factors including HIF-1α. They target the TCA cycle enzyme, IDH3, and drop the levels of α-KG. They also target CUL2 and inhibit the formation of the VCBCR complex. Collectively, miR-424(322)/-503 stabilize HIF-1α and enhance cellular response to hypoxia