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.

中文翻译：

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lncRNA GHET1 通过 EZH2/LSD1 介导的 MT2A 表观遗传抑制调节先兆子痫

先兆子痫（PE）通常被定义为新发高血压伴蛋白尿或其他器官损伤。在此，研究了长非编码RNA（lncRNA）胃癌高表达转录物1（GHET1）在PE过程中的作用和机制。使用定量实时聚合酶链反应 (qRT-PCR) 评估 PE 妊娠中 GHET1 的表达。分别通过细胞计数试剂盒-8 (CCK-8)、集落形成、5-乙炔基-2'-脱氧尿苷 (EdU) 测定和流式细胞术评估绒毛外滋养层的增殖和细胞周期。通过伤口愈合、Transwell 系统和管形成测定来测量滋养细胞的迁移、侵袭和网络形成。RNA 免疫沉淀 (RIP)、RNA Pull-down 和染色质免疫沉淀 (ChIP) 测定用于确认分子相互作用。PE患者胎盘中GHET1显着减少。GHET1在体外促进绒毛外滋养细胞的增殖和细胞周期，以及迁移、侵袭和网络形成。金属硫蛋白2A（MT2A）作为GHET1的下游效应子，在PE中与GHET1呈负相关。GHET1 直接与 zeste 2 多梳抑制复合物 2/赖氨酸特异性脱甲基酶 1 (EZH2/LSD1) 结合。敲除 GHET1 通过招募 EZH2 和 LSD1 减少了 MT2A 启动子区域中 H3K27me3 和 H3K4me2 的占据。MT2A 敲低逆转了 GHET1 抑制介导的生物学功能。GHET1 通过 EZH2/LSD1 介导的 PE 中 MT2A 表观遗传抑制来调节绒毛外滋养层表型。