Overexpressed IncRNA GATA3-AS1 in Preeclampsia and Its Effects on Trophoblast Proliferation and Migration by the miR-488-3p/ROCK1 Axis.

ABSTRACT

Recently, dysregulation of long noncoding RNAs (lncRNAs) has been reported to be involved in the pathogenesis of preeclampsia (PE). Here, the role and molecular mechanisms of lncRNA GATA3 antisense RNA 1, GATA3-AS1 in PE were explored. The expression of GATA3-AS1, miR-488-3p and Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) in placental tissues from patients with PE was measured by reverse transcription quantitative PCR (RT-qPCR). Proliferation, migration, invasion, and apoptosis of trophoblast cells were examined by 5-ethynyl-2'-deoxyuridine (EdU), wound healing, Transwell, and flow cytometry analyses. The subcellular localization of GATA3-AS1 in trophoblast cells was determined by fluorescent hybridization (FISH) assay. The interactions among GATA3-AS1, miR-488-3p and ROCK1 were identified by luciferase reporter and RNA pulldown assays. Our results showed that GATA3-AS1 and ROCK1 were overexpressed while miR-488-3p was downregulated in placental samples with PE. Functionally, GATA3-AS1 overexpression promoted trophoblast cell apoptosis and inhibited cell proliferation, migration, and invasion. Mechanically, GATA3-AS1 acted as a molecular sponge of miR-488-3p and miR-488-3p targeted ROCK1 in trophoblast cells. In rescue assays, ROCK1 overexpression or miR-488-3p downregulation reversed the effects of GATA3-AS1 silencing on trophoblast cell phenotypes. GATA3-AS1 is overexpressed in PE and promotes PE progression by the miR-488-3p/ROCK1 axis.