LncRNA MEG3 Inhibits Trophoblast Invasion and Trophoblast‐mediated VSMC Loss in Uterine Spiral Artery Remodeling
Molecular Reproduction and Development(2019)
Abstract
Extravillous trophoblasts (EVTs) migrate into uterine decidua and induce vascular smooth muscle cell (VSMC) loss through mechanisms thought to involve migration and apoptosis, achieving complete spiral artery remodeling. Long noncoding RNA maternally expressed gene 3 (MEG3) can regulate diverse cellular processes, such as proliferation and migration, and has been discovered highly expressed in human placenta tissues. However, little is known about the role of MEG3 in modulating EVT functions and EVT‐induced VSMC loss. In this study, we first examined the location of MEG3 in human first‐trimester placenta by in situ hybridization. Then, exogenous upregulation of MEG3 in HTR‐8/SVneo cells was performed to investigate the effects of MEG3 on EVT motility and EVT capacity to displace VSMCs. Meanwhile, the molecules mediating EVT‐induced VSMC loss, such as tumor necrosis factor‐α (TNF‐α), Fas ligand (FasL), and tumor necrosis factor‐α‐related apoptosis‐inducing ligand (TRAIL) were detected at transcriptional and translational levels. Finally, VSMCs were cocultured with MEG3‐upregulated HTR‐8/SVneo to explore the role of MEG3 on EVT‐mediated VSMC migration and apoptosis. Results showed that MEG3 was expressed in trophoblasts in placental villi and decidua, and MEG3 enhancement inhibited HTR‐8/SVneo migration and invasion. Meanwhile, the displacement of VSMCs by HTR‐8/SVneo and the expression of TNF‐α, FasL and TRAIL in HTR‐8/SVneo were reduced following MEG3 overexpression in HTR‐8/SVneo. Furthermore, HTR‐8/SVneo with MEG3 upregulation impaired VSMC migration and apoptosis. The PI3K/Akt pathway, which is possibly downstream, was inactivated in MEG3‐upregulated HTR‐8/SVneo. These findings suggest that MEG3 might be a negative regulator of spiral artery remodeling via suppressing EVT invasion and EVT‐mediated VSMC loss.
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Key words
lncRNA maternally expressed gene 3 (MEG3),spiral artery remodeling,trophoblast,vascular smooth muscle cell (VSMC) loss
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