Dysregulated Expression of RPS4Y1 (Ribosomal Protein S4, Y-Linked 1) Impairs STAT3 (Signal Transducer and Activator of Transcription 3) Signaling to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia.

Abstract

Normal placentation and a successful pregnancy depend on appropriate trophoblast cell migration and invasion. Inadequate trophoblast invasion and impaired spiral artery remodeling may lead to pregnancy-related disorders, such as preeclampsia. RPS4Y1 (ribosomal protein S4, Y-linked 1) is a member of the S4E family of ribosomal proteins. In this study, we found that RPS4Y1 levels were upregulated in placental samples collected from preeclamptic patients, when compared with the normotensive pregnant women. In vitro, inhibition of RPS4Y1 induced trophoblast cell invasion, promoted placental explant outgrowth, and increased STAT3 (signal transducer and activator of transcription 3) phosphorylation along with elevated expression of N-cadherin and vimentin. Conversely, overexpression of RPS4Y1 results in reduced trophoblast cell invasion and decreased STAT3 phosphorylation. In addition, the suppression of RPS4Y1 promotes trophoblast cell invasion, which could be abolished by the STAT3 knockdown. Meanwhile, we observed reductions of STAT3 phosphorylation expression in preeclampsia patients. Collectively, these results demonstrate that the level of RPS4Y1 expression may be associated with preeclampsia by affecting trophoblast cell migration and invasion via the STAT3/epithelial-mesenchymal transition pathway.