FOXO1 modulates the biofunctions of trophoblast cells in preeclampsia via the DUSP9/p38/JNK signaling pathway

Background Preeclampsia (PE) is currently one of the major causes threatening the health and leading to death of pregnant women and fetuses. The onset of PE is attributed to cellular biological dysfunction resulting from the disruption of the molecular regulatory network in the trophoblast cells. We discovered that FOXO1 was downregulated in the placenta of preeclampsia. Methods In order to delve deeper into the involvement of FOXO1 in the development of preeclampsia, trophoblast cell lines were generated with manipulated levels of FOXO1, either through overexpression or knockdown, to elucidate its biological function and underlying mechanisms. Results The expression level of FOXO1 is positively correlated with the invasive, migratory, and proliferative abilities of trophoblast cells. Transcriptome sequencing analysis revealed DUSP9 as a potential target gene of FOXO1. The suppression of DUSP9 expression has been shown to markedly diminish the invasive, migratory, and proliferative abilities of trophoblast cells. Silencing DUSP9 in trophoblast cells that exhibit elevated levels of FOXO1 can attenuate their physiological functions. We found that overexpression/inhibition of FOXO1 can correspondingly suppress/activate the p38/JNK signaling pathway. Notably, the inhibition of DUSP9 in the context of FOXO1 overexpression can activate the p38/JNK signaling pathway. Conclusions FOXO1 modulates the biofunctions of trophoblast cells in preeclampsia via the DUSP9/p38/JNK signaling pathway.