Department of Obstetrics, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China.
Bioengineered. 2021 Dec;12(1):6617-6628. doi: 10.1080/21655979.2021.1974808.
Preeclampsia (PE) is a huge threat to pregnant women. Our previous study demonstrated that long non-coding RNA (lncRNA) NR_002794 was highly expressed in placentas of PE patients and could regulate the phenotypes of trophoblast cells. However, the downstream regulatory mechanisms of NR_002794 remain unknown. In this text, some potential downstream targets or signaling pathways of NR_002794 were identified through RNA sequencing (RNA-seq) and bioinformatics analysis in SWAN71 trophoblast cells. Western blot assay demonstrated that NR_002794 inactivated protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways and activated cell apoptotic signaling in SWAN71 cells. Both RNA-seq and reverse transcription-quantitative PCR (RT-qPCR) outcomes showed that NR_002794 up-regulation could notably inhibit the expression of C-C motif chemokine ligand 4 like 2 (CCL4L2), interleukin 15 receptor subunit alpha (IL15RA), interleukin 32 (IL32), and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1), while NR_002794 knockdown induced these gene expressions in SWAN71 cells. CCK-8, BrdU, Transwell, wound healing, and flow cytometry analyses showed that NR_002794 inhibited cell proliferation and migration and induced cell apoptosis through down-regulating TIE1 in SWAN71 cells. In conclusion, lncRNA NR_002794 could exert its functions by regulating AKT and ERK1/2 pathways and TIE1 expression in human trophoblast cells.
子痫前期 (PE) 是孕妇面临的巨大威胁。我们之前的研究表明，长链非编码 RNA (lncRNA) NR_002794 在 PE 患者的胎盘中高度表达，可调节滋养细胞的表型。然而，NR_002794 的下游调控机制尚不清楚。在本研究中，通过 SWAN71 滋养细胞的 RNA 测序 (RNA-seq) 和生物信息学分析，鉴定了 NR_002794 的一些潜在下游靶标或信号通路。Western blot 检测结果表明，NR_002794 可使蛋白激酶 B (AKT) 和细胞外信号调节激酶 1/2 (ERK1/2) 通路失活，并激活 SWAN71 细胞的细胞凋亡信号。RNA-seq 和逆转录定量聚合酶链式反应 (RT-qPCR) 的结果均显示，NR_002794 的上调可显著抑制 C-C 基序趋化因子配体 4 样 2 (CCL4L2)、白细胞介素 15 受体亚单位 α (IL15RA)、白细胞介素 32 (IL32) 和含免疫球蛋白样和表皮生长因子样结构域酪氨酸激酶 1 (TIE1) 的表达，而 NR_002794 的下调则会诱导 SWAN71 细胞中这些基因的表达。CCK-8、BrdU、Transwell、划痕愈合和流式细胞术分析表明，NR_002794 通过下调 TIE1 抑制 SWAN71 细胞的增殖和迁移，并诱导细胞凋亡。综上所述，lncRNA NR_002794 可通过调节 AKT 和 ERK1/2 通路及 TIE1 在人滋养细胞中的表达发挥功能。
