先兆子痫（PE）通常被定义为新发高血压伴有尿蛋白或其他器官损伤。本研究旨在研究长链非编码RNA（lncRNA）胃癌高表达转录本1（GHET1）在PE发生过程中的作用和机制。采用定量实时聚合酶链反应（qRT-PCR）评估PE妊娠中GHET1的表达。通过细胞计数试剂盒-8（CCK-8）、克隆形成、5-乙炔基-2'-脱氧尿苷（EdU）实验和流式细胞术，评估绒毛外胚层细胞的增殖和细胞周期。采用划痕愈合、跨膜实验和管状形成实验测量绒毛外胚层细胞的迁移、侵袭和网络形成能力。采用RNA免疫沉淀（RIP）、RNA拉下和染色质免疫沉淀（ChIP）试验确认了分子相互作用。PE患者的胎盘中GHET1显著降低。GHET1促进了绒毛外胚层细胞的增殖和细胞周期过程，并在体外促进了细胞迁移、侵袭和网络形成。金属硫蛋白 2A（MT2A）作为GHET1的下游效应物，在PE中与GHET1呈负相关。GHET1直接与Zeste 2多组蛋白抑制复合物2/赖氨酸特异性去甲基化酶1（EZH2/LSD1）结合。抑制GHET1能减少EZH2和LSD1在MT2A启动子区域的H3K27me3和H3K4me2的结合能力。MT2A的抑制逆转了GHET1介导的生物功能抑制作用。在PE中，GHET1通过EZH2/LSD1介导的MT2A表观遗传抑制来调节绒毛外胚层细胞表型。© 2023 Wiley Periodicals LLC.

Pre-eclampsia (PE) is usually defined as new-onset hypertension with albuminuria or other organ damage. Herein, the role and mechanism of long noncoding RNA (lncRNA) gastric carcinoma high expressed transcript 1 (GHET1) during PE are investigated. Expression of GHET1 in PE pregnancies was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and cell cycle of extravillous trophoblasts were assessed by Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) assays, and flow cytometry, respectively. Migration, invasion, and network formation of trophoblasts were measured by wound healing, transwell system, and tube formation assays. RNA immunoprecipitation (RIP), RNA pull-down, and chromatin immunoprecipitation (ChIP) assays were used to confirm the molecular interaction. GHET1 was markedly decreased in the placenta of PE patients. GHET1 promoted the proliferation and cell cycle of extravillous trophoblasts, as well as migration, invasion, and network formation in vitro. Metallothionein 2A (MT2A) functioned as a downstream effector of GHET1, which was negatively correlated with GHET1 in PE. GHET1 directly bound with zeste 2 polycomb repressive complex 2/lysine-specific demethylase 1 (EZH2/LSD1). Knockdown of GHET1 reduced the occupancies of H3K27me3 and H3K4me2 in the MT2A promoter region by recruiting EZH2 and LSD1. MT2A knockdown reversed GHET1 inhibition mediated biological functions. GHET1 regulates extravillous trophoblastic phenotype via EZH2/LSD1-mediated MT2A epigenetic suppression in PE.© 2023 Wiley Periodicals LLC.