1. Academic Validation
  2. Stanniocalcin2 inhibits the epithelial-mesenchymal transition and invasion of trophoblasts via activation of autophagy under high-glucose conditions

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

  • Mol Cell Endocrinol. 2022 May 1;547:111598. doi: 10.1016/j.mce.2022.111598.
Rujie Lai 1 Lulu Ji 1 Xiaoli Zhang 2 Yating Xu 1 Yu Zhong 1 Liying Chen 1 Hanyang Hu 3 Lin Wang 4
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
  • 2 Department of Ultrasound Imaging, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 3 Department of Histology and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China. Electronic address: huhanyang923@163.com.
  • 4 Department of Histology and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. Electronic address: lin.wang@whu.edu.cn.
Abstract

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.

Keywords

Autophagy; Epithelial-mesenchymal transformation; GDM; Stanniocalcin2; Trophoblast invasion.

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