Stanniocalcin2 inhibits the epithelial-mesenchymal transition and invasion of trophoblasts via activation of autophagy under high-glucose conditions

Maternal pregnancy hyperglycemia is often accompanied by placental dysfunction. During placental development, epithelial-mesenchymal transition (EMT) contributes to the transformation of relatively noninvasive trophoblasts into highly invasive extravillous trophoblasts (EVTs). However, the specific role of EMT in placentas under hyperglycemia environments remains relatively unexplored. Stanniocalcin2 (STC2) regulates EMT in many cancers. In this study, we first demonstrated that STC2 expression was upregulated in GDM placenta. We found that STC2 activated autophagy and suppressed EMT in high-glucose-treated EVTs and was associated with a lack of invasiveness. Specifically, STC2 inhibited the interactions between p62/SQSTM1 (p62) and EMT transcription factors to promote the degradation of Twist1 and Snail via a proteasome-dependent pathway. Furthermore, the PI3K/AKT/AMPK signaling pathway was involved in the regulation of autophagy and EMT by STC2. Taken together, our results reveal that STC2 may serve as a potential prognostic biomarker in GDM and sheds light on the regulatory mechanisms of trophoblast invasion.

Automated summary

Maternal pregnancy hyperglycemia is often accompanied by placental dysfunction. This study found that the upregulation of Stanniocalcin2 (STC2) expression in gestational diabetes mellitus (GDM) placentas was associated with autophagy activation and EMT suppression, leading to decreased invasiveness of extravillous trophoblasts (EVTs).