The MEG3 lncRNA promotes trophoblastic cell growth and invasiveness in preeclampsia by acting as a sponge for miR-21, which regulates BMPR2 levels

Abstract

Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality in pregnant women. This study aimed to investigate the potential impact and regulatory mechanisms of bone morphogenetic protein receptor 2 (BMPR2) on the progression of PE. We obtained placental tissues from pregnant women with PE and normal pregnant women, and the results showed that BMPR2 was expressed at low levels in the tissue from PE women. Genetic knockdown of BMPR2 increased the proliferation and invasion of cultured trophoblast cells, whereas its overexpression reduced these characteristics. Bioinformatics analysis and luciferase reporter gene assays confirmed that BMPR2 is a direct target of miR-21. Overexpression of a miR-21 inhibitor promoted the growth and invasiveness of trophoblast cells, whereas the opposite results were observed for the miR-21 mimic. Furthermore, miR-21 was sponged by the lncRNA MEG3, and shRNA inhibition of MEG3 reduced trophoblast cell growth and invasiveness. miR-21 was upregulated in the tissues from PE women, whereas MEG3 was downregulated, and the two were negatively correlated. Collectively, this study demonstrates that the lncRNA MEG3 acts as a sponge for miR-21, which regulates BMPR2 expression and promotes trophoblast cell proliferation and invasiveness, thereby preventing the development of PE. These findings provide novel insight into a targeted therapy that could be used to treat or prevent the development of PE.

Identification of LncRNA-miRNA-mRNA ceRNA network in hypoxia-induced HTR-8/SVneo cells for preeclampsia

“…Studies have shown that MEG3 affects trophoblast invasion and apoptosis by sponging miR-21, miR-210, and miR770. [50][51][52] SNHG16 was first described as an oncogenic factor. [53] It has been reported that SNHG16 regulates the proliferation, invasion, and migration of multiple cells.…”

High glucose inhibits neural differentiation by excessive autophagy <em>via</em> peroxisome proliferator-activated receptor gamma

“…This procedure was performed as in our previous report. 50 Protein extracts from cells were prepared in RIPA buffer (Beyotime) containing 1% NP-40 (Beyotime) and a cocktail of protease and phosphatase inhibitors (Beyotime). Protein concentrations were determined using the Bio-Rad protein assay (Bio- Rad, Hercules, CA, USA; 500-0006).…”