Department of Gynaecology, Hebei General Hospital, Shijiazhuang, 050051, China.
Crit Rev Eukaryot Gene Expr. 2023;33(3):47-60. doi: 10.1615/CritRevEukaryotGeneExpr.2022045376.
Recurrent miscarriage (RM) is a frustrating and complex pregnancy disorder and long noncoding RNAs (lncRNAs) modulate susceptibility to RM. This study expounded on the role of specificity protein 1 (SP1) in functions of chorionic trophoblast and decidual cells via regulating lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1). Chorionic villus tissues and decidual tissues of RM patients and normal pregnant women were collected. Real-time quantitative polymerase chain reaction and Western blotting revealed that SP1 and NEAT1 were downregulated in trophoblast and decidual tissues of RM patients, and the Pearson correlation analysis detected that they were positively correlated in expression level. Chorionic trophoblast and decidual cells of RM patients were isolated and intervened by vectors over-expressing SP1 or NEAT1 siRNAs. Thereafter, the cell counting kit-8, Transwell, flow cytometry assays detected that SP1 overexpression accelerated trophoblast cell proliferation, invasion, and migration, meanwhile, enhancing decidual cell proliferation while repressed apoptosis. Next, the dual-luciferase and Chromatin immunoprecipitation assays showed that SP1 bound to the NEAT1 promoter region and further activated NEAT1 transcription. Silencing NEAT1 reversed the efforts of SP1 overexpression on the functions of trophoblast and decidual cells. Overall, SP1 activated NEAT1 transcription, accelerating trophoblast cell proliferation, invasion, and migration and mitigating decidual cell apoptosis.
复发性流产（RM）是一种令人沮丧且复杂的妊娠疾病，长链非编码 RNA（lncRNA）调节 RM 的易感性。本研究通过调节核斑蛋白组装转录物 1（NEAT1）来阐述特异性蛋白 1（SP1）在绒毛膜滋养层和蜕膜细胞功能中的作用。收集 RM 患者和正常孕妇的绒毛组织和蜕膜组织。实时定量聚合酶链反应和 Western blot 显示，SP1 和 NEAT1 在 RM 患者的滋养层和蜕膜组织中下调，Pearson 相关分析检测到它们在表达水平上呈正相关。分离 RM 患者的绒毛滋养层和蜕膜细胞，并通过过表达 SP1 或 NEAT1 siRNA 的载体进行干预。此后，细胞计数试剂盒-8、Transwell、流式细胞术检测显示 SP1 过表达加速了滋养层细胞的增殖、侵袭和迁移，同时增强了蜕膜细胞的增殖，同时抑制了细胞凋亡。接下来，双荧光素酶和染色质免疫沉淀测定显示 SP1 结合到 NEAT1 的启动子区域，并进一步激活了 NEAT1 的转录。沉默 NEAT1 逆转了 SP1 过表达对滋养层和蜕膜细胞功能的影响。总的来说，SP1 激活了 NEAT1 的转录，加速了滋养层细胞的增殖、侵袭和迁移，并减轻了蜕膜细胞的凋亡。
