The Lnc RNA SPRY4-IT1 Modulates Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition

Dong

J Biochem & Molecular Tox

et al. 2020

Dysfunction of trophoblast metastasis into the endometrium is the main cause of pre‐eclampsia (PE); however, the factors affecting this process are still unclear. In this study, we found that endoplasmic reticulum protein 29 (ERp29), one molecular chaperone of the endoplasmic reticulum, was aberrantly upregulated in the placenta of pre‐eclamptic patients compared with healthy controls. Then, an in vitro study using human extravillous trophoblast HTR‐8/SVneo cells showed that ERp29 upregulation could inhibit the migratory and invasive ability of HTR‐8/SVneo cells, while ERp29 downregulation had the opposite effect. Mechanical experiments confirmed that ERp29 blocked trophoblast metastasis via inhibiting the process of epithelial‐mesenchymal transition and affecting the Wnt/β‐catenin signaling pathway. In conclusion, this study revealed the important role of ERp29 in trophoblast metastasis and improved the mechanical understanding of PE occurrence.

Section: Discussionmentioning

confidence: 99%

ERp29 affects the migratory and invasive ability of human extravillous trophoblast HTR‐8/SVneo cells via modulating the epithelial‐mesenchymal transition

Dong

J Biochem & Molecular Tox

et al. 2020

Journal Cellular Physiology

“…Accumulating researchers have indicated that lncRNAs may play a pivotal role in the development of various diseases, including pre‐eclampsia (Chen et al, ; Gao et al, ; Zhang et al, ; Zou & Sun, ; Zuo et al, ). Since childbirth is the only treatment of pre‐eclampsia, it is reasonable to hypothesize that structural and functional alterations in the placenta promote to the pathogenesis of pre‐eclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…lncRNA is broadly defined as transcribed, but not translated, RNA molecules greater than 200 nucleotides in length (Ørom & Shiekhattar, ), has been shown to be involved in the development of multiple diseases (Faghihi et al, ; Gupta et al, ; Lin, Maeda, Liu, Karin, & Edgington, ; Tano et al, ). Previous studies suggest that lncRNAs may be involved in the development of pre‐eclampsia by altering placental trophoblast the proliferation, invasion, and migration of placental trophoblast cells (Gao et al, ; Zhang et al, ; Zuo et al, ). Obviously, targeted to explore the mechanism of lncRNA in early‐onset pre‐eclampsia, help to solve this clinical problem.…”

Section: Introductionmentioning

confidence: 99%

The long noncoding RNA uc.294 is upregulated in early‐onset pre‐eclampsia and inhibits proliferation, invasion of trophoblast cells (HTR‐8/SVneo)

Song

et al. 2018

Recently, a large number of long noncoding RNAs (lncRNAs) have been reported in human diseases that are evolutionarily conserved and are likely to play a role in many biological events including pre‐eclampsia. In our previous research, we selected thousands of lncRNAs for their relationship with early‐onset pre‐eclampsia. Among these lncRNAs, a lncRNA named uc.294 attracted our attention, was once reported to specifically be expressed at a high level in the early‐onset of pre‐eclampsia. This study aims to investigate the function of uc.294 in early‐onset pre‐eclampsia and the possible mechanism. The uc.294 expression level in early‐onset pre‐eclampsia or in normal placenta tissues was evaluated by quantitative real‐time polymerase chain reaction. To detect the proliferation, invasion, and apoptosis capacity of the trophoblast cells, we performed the Cell Counting Kit‐8 assay, transwell assay, and flow cytometry, respectively. Here we report, for the first time, that uc.294 inhibits proliferation, invasion, and promotes apoptosis of trophoblast cells HTR‐8/SVneo by working in key aspects of biological behaviors. However, how uc.294 acts to regulate gene functions in early‐onset pre‐eclampsia needs further exploration.

J Cellular Molecular Medi

“…26 Both assays followed a similar protocol except that the 26 Both assays followed a similar protocol except that the …”

Section: Cell Migration and Invasion Assaysmentioning

confidence: 99%

“…Cell migration and invasion assays were performed as previously reported. 26 Both assays followed a similar protocol except that the transwell insert (Costar, Cambridge, MA, USA) was pre-coated with Matrigel (BD Biosciences, Beit-Ha' Emek, Israel) for the cell invasion assay but not for the cell migration assay. Briefly, 3-5×10 4 HTR-8/ SVneo cells were cultivated in media without FBS in the upper chamber of the transwell insert, whereas media containing FBS was added to the lower chamber.…”

Section: Cell Migration and Invasion Assaysmentioning

confidence: 99%

The role of NUDT21 in microRNA‐binding sites of EZH2 gene increases the risk of preeclampsia

Xiao

Zhao²,

Huang

et al. 2019

Objectives Preeclampsia (PE) is a major cause of mortality and morbidity among pregnant mothers and their fetuses worldwide. Recent studies have shown that several microRNAs (miRNAs) play crucial role in pathogenesis of PE patients; however, the mechanisms responsible for differences in miRNA function in PE largely remain to be determined. Materials and Methods We studied that NUDT21 expression was markedly increased, whereas EZH2 was decreased in placental samples from patients with PE. We identified NUDT21 as an interaction partner of enhancer of zeste homologue 2 (EZH2). NUDT21 co‐localized with EZH2 in the human trophoblast cell line, HTR‐8/SVneo and NUDT21 was shown to bind to EZH2 in RNA immunoprecipitation assays. NUDT21 has previously been reported to be involved in alternative polyadenylation; thus, the interaction between NUDT21 and EZH2 may play an important role in the crosstalk between alternative polyadenylation (APA) and miRNA‐mediated gene silencing in PE. Results In the human trophoblast cell line HTR‐8/SVneo, loss‐of‐function assays indicated that knockdown of NUDT21 suppressed cell proliferation, migration and tube formation. Furthermore, functional studies showed that NUDT21 elongated the 3'‐UTR of mRNAs thereby exposing more miRNA binding sites (including miR138 and miR363), which enhanced the efficiency of miRNA‐mediated gene silencing and promoted EZH2 binding. Conclusions This is the first report about the relationship of NUDT21 and EZH2. The data indicate that the aberrant expression of NUDT21 contributes to PE by targeting 3'‐UTR of EZH2 mRNA. These findings may provide novel targets for future investigations into therapeutic strategies for PE.