LncRNA TDRG1/miR‐214‐5p axis affects preeclampsia by modulating trophoblast cells

Abstract

Because of limited treatment options, preeclampsia (PE) is the leading cause of perinatal morbidity and mortality worldwide. Recently, lncRNA TDRG1 is reported to be aberrantly down-regulated in PE placenta, and the abnormal expression of TDRG1 might play a key or partial role in PE development. In this study, we found that TDRG1 was significantly down-regulated in PE placenta compared with the normal placenta.The cell proliferation, migration, invasion, and cell cycle were explored by CCK-8, wound-healing, transwell, and flow cytometer assay, respectively. Experimental results showed that TDRG1 accelerated the proliferation, migration, and invasion of trophoblast cells. Dual-luciferase reporter assays confirmed that TDRG1 could bind to miR-214-5p. Besides, knockdown of TDRG1 suppressed the cell proliferation, migration, and invasion, while knockdown of miR-214-5p reversed the effect. Jagged1 and Notch1 were negatively regulated by miR-214-5p while positively modulated by TDRG1. In conclusion, TDRG1 promoted trophoblast cells viability and invasion by negatively regulating miR-214-5p expression, contributing to a better understanding of PE pathogenesis and providing new light on TDRG1-directed diagnosis and treatment.Significance of the study: In this work, we observed that TDRG1 was able to promote cell proliferation, migration, and invasion cells by suppressing the expression of miR-214-5p and regulating the Notch signalling pathway in trophoblast cells. As far as we know, the effect of TDRG1/miR-214-5p axis on cell viability, migration, and invasion of trophoblast cells was firstly introduced. Our findings provided a better understanding of the mechanism of PE. Moreover, it is reasonable to believe that TDRG1 may be employed as a strategy to treat PE in the future. K E Y W O R D SmiR-214-5p, Notch1, preeclampsia, TDRG1, trophoblast cells

Increased LINC00922 in preeclampsia regulates the proliferation, invasion, and migration of placental trophoblast cells

“…For example, lncRNA TDRG1 is abnormally downregulated in the placenta in PE, and overexpression of TDRG1 can promote the proliferation, migration, and invasion of trophoblast cells, while knockdown of TDRG1 can inhibit these processes. Studies on molecular mechanisms have shown that TDRG1 can bind to miR-214-5p, which can regulate the Jagged1 and Notch1 signaling pathways (10). In addition, lncRNAs may be used as targets for predicting and diagnosing PE in the future.…”

ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis

“…Previous studies have revealed that a series of lncRNAs are associated with PE by inhibiting the proliferation, migration, and invasion of trophoblast cells, promoting angiogenesis and inducing apoptosis. Among them, the expression of lncRNA Gas5 [24], lncRNA DLX6-AS1 [25], and lncRNA Linc00261 [26] is upregulated in PE, while the expression of lncRNA MALAT1 [27], lncRNA LINC00511 [28], and lncRNA TDRG1 [29] is downregulated.…”

Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) Represses Proliferation of Trophoblast Cells in Rats with Preeclampsia via the MicroRNA-373/FLT1 Axis

“…Inflammation, oxidative stress, and placental trophoblast cells have all been closely linked to PE. The lack of migration and invasion of trophoblast cells has been found to contribute to inadequate remodeling of spiral arteries, the major driver of PE pathogenesis [ 15 ]. Furthermore, lncRNAs have been shown to play pivotal roles in the modulation of trophoblast cell function and the incidence of PE [ 16 , 17 ].…”