title: 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.
authors.affiliation: Department of Obstetrics, Gynecology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, 210029, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Zou
authors.forename: Wenqi
authors.initials: W
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zuo
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.forename: Lizhou
authors.initials: L
authors.lastname: Sun
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics*; D014327:Trophoblasts / Q000502:physiology*
chemical_list: C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: APOPTOSIS; LONG NON-CODING RNA MEG3; MIGRATION; PREECLAMPSIA; TROPHOBLAST