UBE3A Inhibits Trophoblast Cell Migration and Invasion by Promoting ITGB1 Degradation and Affecting PI3K/AKT Signaling.

Preeclampsia (PE) is an obstetric disease that is characterized by reduced migration and invasion of placental trophoblast cells. Here, the effects of the E3 ubiquitin ligase UBE3A on the migration and invasion of trophoblast cells were evaluated. RT-qPCR and Western blotting were used to measure the expression of genes and proteins. Immunohistochemical (IHC) staining was used to determine UBE3A and ITGB1 levels in the placental tissues of PE patients. Cell viability was evaluated with a CCK-8 assay. Wound healing and Transwell assays were used to evaluate cell migration and invasion, respectively. Cell cycle progression and apoptosis were analyzed by flow cytometry. Co-immunoprecipitation (Co-IP) was used to verify molecular interactions. Our results revealed that the mRNA and protein levels of UBE3A were upregulated, whereas ITGB1 expression was downregulated in the placental tissues of PE patients. Depletion of UBE3A promoted the migration and invasion of HTR-8/SVneo cells while inhibiting apoptosis. The phosphorylation of PI3K and AKT increased after UBE3A was silenced. Mechanistically, UBE3A induced the ubiquitination and degradation of ITGB1. Functionally, UBE3A reduced cell migration and invasion, as well as induced apoptosis by negatively regulating ITGB1 mediating PI3K/AKT signaling. In summary, our results revealed that UBE3A hindered the migration and invasion of trophoblast cells by facilitating ITGB1 degradation and affecting PI3K/AKT signaling, providing a new therapeutic target for PE treatment.