METTL14 promotes trophoblast dysfunction by elevating SZRD1 expression in an m6A-dependent manner.

Preeclampsia, a common hypertensive pregnancy disorder associated with shallow trophoblast invasion, is a leading cause of perinatal and maternal mortality worldwide. Many studies have indicated that genes are differentially expressed between normal and diseased states. This study found that SUZ RNA binding domain containing 1 (SZRD1) expression was increased in placenta from preeclamptic pregnancies. However, the role and mechanism of SZRD1 in patients with preeclampsia are unclear. Gene expression was determined by RT-qPCR and Western blot. Cell proliferation, apoptosis, migration, invasion, and angiogenesis were assessed using EdU, flow cytometry, wound healing, transwell, and tube formation assays. The interaction between Methyltransferase-like 14 (METTL14) and SZRD1 was analyzed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RIP assay. SZRD1 and METTL14 were highly expressed in placenta from preeclamptic pregnancies (n = 30) compared with normal tissues (n = 30) (p < 0.001). By using HTR-8/SVneo trophoblast cells, the silencing of SZRD1 could promote cell proliferation (p < 0.01), migration (p < 0.05), invasion (p < 0.01), angiogenesis (p < 0.01), and hinder cell apoptosis (p < 0.01) in vitro. At the molecular level, METTL14 enhanced the stability of SZRD1 mRNA via m6A methylation. The METTL14-mediated stabilization of SZRD1 mRNA could exacerbate the dysfunction in HTR-8/SVneo cells associated with preeclampsia. These findings highlight the potential of targeting the METTL14/SZRD1 axis as a therapeutic strategy for managing preeclampsia.