Long Noncoding RNA 00473 Is Involved in Preeclampsia by LSD1 Binding-Regulated TFPI2 Transcription in Trophoblast Cells

Abstract

Preeclampsia (PE) is a syndrome manifested by high blood pressure that could develop in the latter half of pregnancy; however, the underlying mechanisms are not understood. Recent evidence points to the function of noncoding RNAs (ncRNAs) as novel regulators of the invasion, migration, proliferation, and apoptosis of trophoblasts involved in the development of placental vasculature. Here, we investigated the role of long intergenic ncRNA 00473 (linc00473) in PE and the associated molecular mechanisms. The expression of linc00473 was downregulated in the placenta of patients with severe PE as revealed by qRT-PCR analysis. In vitro, linc00473 knockdown in trophoblast cell lines HTR-8/SVneo, JAR, and JEG3 significantly inhibited cell proliferation and promoted apoptosis, whereas linc00473 overexpression stimulated trophoblast proliferation. The mechanistic insights were provided by RNA-seq and qRT-PCR, which revealed that linc00473 could regulate the transcription of genes relevant to cell growth, migration, and apoptosis. In particular, linc00473 inhibited the expression of tissue factor pathway inhibitor 2 (TFPI2) through binding to lysine-specific demethylase 1 (LSD1). These results indicate that linc00473 could be involved in the pathogenesis and development of PE and may be a candidate biomarker as well as therapeutic target for this disease.

Long Noncoding RNA in Preeclampsia: Transcriptional Noise or Innovative Indicators?

“…The decreased level of EGFR Antisense RNA1 (EGFR-AS1) in PE had the potential to decrease the level of EGFR in trophoblast cells and the phosphorylation levels of downstream proteins in JAK/STAT signal pathway, followed by inducing the occurrence of PE [57]. The level of linc00473 was decreased in the placental tissues of severe PE women, linc00473 downregulation in trophoblast cells substantially reduced cell proliferation, together with increasing cell apoptosis, while linc00473 upregulation increased cell proliferation through the attenuation of tissue factor pathway inhibitor 2 (TFPI2) by combing to LSD1 [58]. LncRNA PVT1 downregulation substantially decreased cell proliferation; besides inducing the cell cycle as well as cell apoptosis, the mechanism of PVT1 was through the regulation of angiopoietin-like 4 (ANGPTL4) as well as Ezh2 [59].…”

Preeclampsia-Associated lncRNA INHBA-AS1 Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells

“… 59 We chose HTR-8SV/neo cells for cellular functional studies because this cell line is widely used in previous studies on the pathogenesis of PE. 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 We overexpressed or knocked out this gene in this placenta-derived trophoblast cell line and found that INHBA-AS1 prohibited the invasion, migration, and proliferation ( Figures 2 A–2D, 3 A, and 3B) and promoted apoptosis ( Figures 3 C and 3D). These results demonstrated that INHBA-AS1 may participate in the pathogenesis of PE through inhibiting trophoblast invasion, migration, and proliferation, which may lead to shallow implantation of the placenta.…”

Identification of long non‑coding RNAs expressed during the�osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells obtained from patients with ONFH

“…In the present study, LINC00473, also known as LNC473, C6orf176, bA142J11.1, and is located in the 6q27 region and LINC00473, was downregulated in the hBMSCs following osteogenic differentiation. It has been found that LINC00473 was involved in the development of a number of diseases including preeclampsia ( 38 ), colorectal cancer ( 39 ), gastric cancer ( 40 ) and others. It has been demonstrated that LINC00473 is involved in the pathogenesis and development of preeclampsia and may be a candidate biomarker, as well as a therapeutic target for preeclampsia ( 38 ).…”

“…It has been found that LINC00473 was involved in the development of a number of diseases including preeclampsia ( 38 ), colorectal cancer ( 39 ), gastric cancer ( 40 ) and others. It has been demonstrated that LINC00473 is involved in the pathogenesis and development of preeclampsia and may be a candidate biomarker, as well as a therapeutic target for preeclampsia ( 38 ). Wang et al found that LINC00473 promoted Taxol resistance via miR-15a in colorectal cancer ( 39 ).…”