Wan Pengyun, Huang Jia, Liu Wenting, Su Xiaoyan, Zhao Bei, Wang Xianggang, Zhao Lu
Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.
Reproductive Health Department, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi Province, People's Republic of China.
Mol Reprod Dev. 2023 Aug-Sep;90(8-9):758-770. doi: 10.1002/mrd.23693. Epub 2023 Aug 7.
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.
子痫前期（PE）通常定义为新发高血压伴蛋白尿或其他器官损害。在此，研究长链非编码RNA（lncRNA）胃癌高表达转录本1（GHET1）在PE发生过程中的作用及机制。采用定量实时聚合酶链反应（qRT-PCR）评估PE妊娠中GHET1的表达。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）检测和流式细胞术评估绒毛外滋养层细胞的增殖和细胞周期。通过伤口愈合、transwell系统和管腔形成试验检测滋养层细胞的迁移、侵袭和网络形成。采用RNA免疫沉淀（RIP）、RNA下拉和染色质免疫沉淀（ChIP）试验来证实分子间相互作用。PE患者胎盘中GHET1明显降低。GHET1促进绒毛外滋养层细胞的增殖和细胞周期，以及体外的迁移、侵袭和网络形成。金属硫蛋白2A（MT2A）作为GHET1的下游效应因子，在PE中与GHET1呈负相关。GHET1直接与zeste 2多梳抑制复合物2/赖氨酸特异性去甲基化酶1（EZH2/LSD1）结合。敲低GHET1通过招募EZH2和LSD1降低MT2A启动子区域H3K27me3和H3K4me2的占有率。敲低MT2A可逆转GHET1抑制介导的生物学功能。在PE中，GHET1通过EZH2/LSD1介导的MT2A表观遗传抑制调节绒毛外滋养层细胞表型。
