WTAP Regulates NCOA4-Mediated Ferroptosis via a YTHDF2-Dependent Mechanism in Preeclampsia

WTAP knockdown alters gene expression in trophoblasts, notably downregulating YTHDF2 and upregulating NCOA4. These changes are linked to disrupted pathways in proliferation, migration, and oxidative stress, and are consistent with abnormal expression patterns observed in preeclampsia placental tissues. Overall design: HTR-8/SVneo trophoblast cells were transfected with siRNAs against WTAP, YTHDF2, and NCOA4 to assess changes in proliferation, migration, and ferroptosis. WTAP expression in PE placentas was evaluated via qRT-PCR and immunohistochemistry. MeRIP-qPCR assessed m6A methylation of NCOA4 mRNA. Ferroptosis markers were analyzed. A PE mouse model was established to examine in vivo effects of YTHDF2 knockdown and NCOA4 overexpression, with or without Ferrostatin-1 treatment, to evaluate therapeutic relevance.