The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3

Abstract

Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE. Loss-function assays indicated that knockdown TUG1 significantly affected cell proliferation, apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1 could affect abundant genes, and then explore the function and regulatory mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays validated that TUG1 can epigenetically inhibit the level of RND3 through binding to EZH2, thus promoting PE development. Therefore, via illuminating the TUG1 mechanisms underlying PE development and progression, our findings might furnish a prospective therapeutic strategy for PE intervention.

Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD

“…The lncRNA taurine‐up‐regulated gene 1 (TUG1), a ~7.1 kb highly conserved lncRNA, was originally identified in taurine‐treated retinal cells. TUG1 has been reported to play critical roles in the progression of many human diseases, such as cancer, aortic valve calcification and pre‐eclampsia . Indeed, TUG1 can regulate gene expression via diverse mechanisms during various biological processes, including inflammatory response.…”

“…TUG1 has been reported to play critical roles in the progression of many human diseases, such as cancer, aortic valve calcification and pre-eclampsia. [8][9][10] Indeed, TUG1 can regulate gene expression via diverse mechanisms during various biological processes, including inflammatory response. Overexpression of TUG1 has been shown to protect the mouse liver against cold-induced injury by inhibiting apoptosis and inflammation, 11 whereas TUG1 knockdown inhibits hyperlipidaemia, decreases inflammatory response and alleviates atherosclerotic lesions.…”

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

“…13 Down-regulation of Nudt21 expression in cells has been reported to lead to changes in alternative poly(A) site utilization for several somatic mRNAs. 28 In this study, we investigated the mechanistic basis for F I G U R E 6 EZH2 is important for trophoblast growth and migration and endothelial cell tube formation. 28 In this study, we investigated the mechanistic basis for F I G U R E 6 EZH2 is important for trophoblast growth and migration and endothelial cell tube formation.…”

“…16,17 Many studies have established that Ezh2 acts as a suppressor of RNA transcription through H3K27me3, include in PE. 28 In this study, we investigated the mechanistic basis for the marked increase in NUDT21 expression in the placentas of pregnant women with PE compared with normal pregnancies. Our research confirmed the interaction between EZH2 and NUDT21 and showed that this interaction plays an important role in the crosstalk between APA and miRNA-mediated gene silencing in PE.…”

Could circRNA be a new biomarker for pre‐eclampsia?

“…Genome‐wide lncRNAs expression patterns indicate numerous lncRNAs extensively expressed in pre‐eclampsia. Previous studies have reported that different expression of lncRNAs in pre‐eclampsia is related to multiple pathways, including trophoblast invasion (Long et al, ), autophagy (Gao et al, ), apoptosis (Song et al, ; Xu et al, ; Zou & Sun, ), proliferation (Cao et al, ; Li et al, ; Xu et al, ), migration, and angiogenesis (Chen et al, ; Yu et al, ; Zhang et al, ). Circular RNAs (circRNAs), as one type of ncRNAs, have been demonstrated to function as a potential regulator of other RNAs transcription like microRNAs (miRNAs).…”