Down‐Regulated Long Non‐Coding RNA MEG3 and its Effect on Promoting Apoptosis and Suppressing Migration of Trophoblast Cells

Abstract

Preeclampsia is characterized by hypertension and proteinuria twenty weeks into pregnancy. Failure of uterine spiral artery remodeling contributes to preeclampsia's development. The development might be associated with trophoblast cells functioning abnormally. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many diseases. Maternally expressed gene 3 (MEG3), one of these lncRNAs, might function as a tumor suppressor. Aberrant expression of MEG3 induces prenatal death, and little is known of MEG3's role in preeclampsia. This study aims to identify the role of lncRNA MEG3 on apoptosis and the migration of human trophoblast cells, and to investigate the involvement of lncRNA MEG3 in pathogenic mechanisms underlying preeclampsia. In this study, we found MEG3 levels were down-regulated by approximately 80% in placental samples collected from preeclamptic patients (n = 30) compared to samples collected from normotensive patients (n = 30) by qRT-PCR analysis. By designing RNA interference species to suppress MEG3 and specific plasmids designed to over-express MEG3, we explored the role of MEG3 on the functions of two trophoblast cell-lines, HTR-8/SVneo and JEG3 cells. Over-expression of MEG3 reduced apoptosis and promoted migration of HTR-8/SVneo and JEG3 cells. Furthermore, inhibition of endogenous MEG3 increased apoptosis and decreased migration of HTR-8/SVneo and JEG3 cells. Additionally, lncRNA MEG3 influenced expression of NF-κB, Caspase-3, and Bax protein expressions in trophoblast cells. Our findings highlight that abnormal levels of lncRNA MEG3 might lead to aberrant conditions in HTR-8/SVneo and JEG3 trophoblast cells, which might be associated with uterine spiral artery remodeling failure and its contribution to preeclampsia.

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

“…Recently, several reports have described the expression profiles of lncRNAs in PE and the association between lncRNAs and the pathology of PE35. In previous studies, we have found aberrant expression of the lncRNA SPRY4-IT124 and MEG3 in PE placentas and have demonstrated their modulatory effects on various biological functions of trophoblast cells36. In the present study, which is based on our previous work, we further verified the inhibitory role of SPRY4-IT1 in EMT-associated events, including invasion and migration of trophoblast cells24.…”

Promotion of trophoblast invasion by lncRNA MVIH through inducing Jun‐B

“…Our previous studies also revealed a panel of lncRNAs that might serve as potential biomarkers for predicting PE . Among these, abnormal expression of SPRY4‐IT1 , a highly conserved lncRNA that is localized in the nucleus, might be predictive of trophoblast metastasis and apoptosis in PE .…”

Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

“…The roles of non-coding RNA (ncRNA), including small ncRNAs and lncRNAs (> 200 nt) have been known for decades [6,7]. It has been shown that lncRNA plays an important role in multiple molecule regulation, such as transcriptional regulation, post-transcriptional regulation, and modification [8][9][10].…”