Role of ARID1A in the Regulation of Human Trophoblast Migration and Invasion.

Abstract

Migration and invasion of trophoblasts is critical for human placental development, trophoblastic differentiation, and pregnancy-associated diseases. AT-rich interactive domain-containing protein 1A (ARID1A), a subunit of the SWI-SNF complex, has been suggested to participate in the regulation of fertility via placental disruption in mice. However, whether ARID1A regulates human placental development and function remains unknown. Here, using human trophoblast-like JEG-3 cell line, we report that ARID1A controls trophoblast cell migration and invasion. Overexpression of ARID1A inhibits JEG-3 cell migration and invasion, whereas knockdown of ARID1A promotes migration and invasion in JEG-3 cells. Mechanistically, while ARID1A reduces JEG-3 cell migration by down-regulation of Snail transcription, it restrains JEG-3 cell invasion by binding to and destabilization of MMP-9 protein. Finally, ARID1A is apparently up-regulated in placental tissues of preeclampsia compared to that of normal pregnancies. Our results thereby imply that ARID1A acts as a critical gene in supporting the physiological function of human mature placenta.