Fig. 10.

The mechanism behind ferroptosis induction in trophoblasts by miR-30b-5p under hypoxia.

miR-30b-5p, which targets the 3′-UTR of Pax3 and SLC7A11 mRNA, inhibits their expression post-transcriptionally. Downregulation of Pax3 is accompanied with low pre-transcriptional efficiency during FPN1 expression. SLC7A11 and FPN1 regulate the import of cystine and the export of iron, respectively, and therefore, a decreased expression of SLC7A11 and FPN1 blocks the synthesis of GSH and results in the accumulation of iron. With the depletion of GSH, the oxidizing power of ROS that was stimulated by hypoxia was further enhanced by liable Fe(II), leading to a massive generation of lipid peroxides and consequent ferroptosis. GSH: glutathione; FPN1: ferroportin 1; LOP: lipid peroxides; TfR: transferrin receptor.