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ABSTRACTIn preeclampsia (PE), preexistent maternal endothelial dysfunction leads to impaired placentation and vascular maladaptation. Long noncoding RNAs (lncRNAs) have been shown to participate in the placentation process. LncRNA fms-related tyrosine kinase 1 pseudogene 1 (FLT1P1) was previously reported to be upregulated in PE. In this study, we verified the effect of FLT1P1and its cognate gene FLT1on trophoblast cell proliferation and angiogenesis by using Cell Counting Kit-8 (CCK-8) assay, tube formation assay, and western blot analysis. Their binding to RNA binding protein dyskeratosis congenita 1 (DKC1) was validated by conducting RNA immunoprecipitation (RIP) and RNA pulldown assays. In this study, knockdown of FLT1P1or FLT1was found to promote cell proliferation and angiogenesis in trophoblasts. In addition, FLT1P1recruited DKC1to stabilize FLT1. Importantly, silencing FLT1P1or DKC1decreased the stability of FLT1. Rescue assays revealed that FLT1overexpression reversed the effect of silenced FLT1P1. Overall, FLT1P1cooperates with DKC1to restrain trophoblast cell proliferation and angiogenesis by targeting FLT1.

Objective The deficient placental blood perfusion caused by the attenuated infiltration of trophoblast cells is a key factor in the occurrence of preeclampsia (PE). Furthermore, the long noncoding (lnc)RNA SNHG12 (small nucleolar RNA host gene 12) can promote the proliferation and metastasis of multiple tumor cells. However, whether lncRNA SNHG12 affects proliferation and metastasis of trophoblast cells is unclear.Methods We examined the level of lncRNA SNHG12 in plasma and placenta of patients with PE and constructed trophoblast cells with overexpressed or knocked down SNHG12. CCK-8, wound healing, and Transwell assays were used to detect alterations in proliferation, migration, and invasion of trophoblast cells. Western blotting was used to detect proteins related to the epithelial–mesenchymal transition (EMT), and cell cycle assays clarified cell cycle distribution.Results LncRNA SNHG12 promoted the proliferation, migration, and invasion of trophoblast cells. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, β-catenin, and vimentin were positively correlated with SNHG12, and expression of E-cadherin was negatively correlated with SNHG12. SNHG12 also promoted the transition of trophoblast cells from G0/G1to S phase.Conclusion Overall, lncRNA SNHG12 promoted the migration and invasion of trophoblast cells by inducing the progression of EMT.