Abstract

The trophoblast apoptosis induced by placental oxidative stress is a contributor to the pathological development of preeclampsia (PE), whereas the molecular mechanism remains unclear. In this study, we explored the role and mechanism of Long non-coding RNA (LncRNA) NEAT1 in trophoblasts apoptosis. In the placenta tissues of PE patients and H₂O₂-treated human trophoblast cell line HTR-8/SVneo, the expressions of LncRNA NEAT1, p53, and estrogen receptor α (ESRα) were increased whereas miR-18a-5p expression was decreased. ESRα expression was up-regulated by LncRNA NEAT1 overexpression and down-regulated by miR-18a-5p overexpression in HTR-8/SVneo cells. LncRNA NEAT1 could release ESRα expression through sponging miR-18a-5p and the transcription of LncRNA NEAT1 was promoted by p53. miR-18a-5p overexpression suppressed H₂O₂-induced cell apoptosis in HTR-8/SVneo cells, while the inhibitory effect of miR-18a-5p overexpression on cell apoptosis was abrogated by LncRNA NEAT1 overexpression. In summary, LncRNA NEAT1 transcription was induced by p53 under oxidative stress condition, the high expression of LncRNA NEAT1 subsequently increased ESRα expression by sponging miR-18a-5p, thus inducing trophoblasts apoptosis.

摘要

胎盘氧化应激诱导的滋养层细胞凋亡是先兆子痫 (PE) 病理发展的一个促成因素，而分子机制尚不清楚。在本研究中，我们探讨了长链非编码 RNA (LncRNA) NEAT1 在滋养层细胞凋亡中的作用和机制。在 PE 患者的胎盘组织中和 H ₂ O ₂处理的人滋养层细胞系 HTR-8/SVneo，LncRNA NEAT1、p53 和雌激素受体 α (ESRα) 的表达增加，而 miR-18a-5p 的表达降低。在 HTR-8/SVneo 细胞中，ESRα 表达被 LncRNA NEAT1 过表达上调，被 miR-18a-5p 过表达下调。LncRNA NEAT1 可通过海绵 miR-18a-5p 释放 ESRα 表达，p53 促进 LncRNA NEAT1 的转录。miR-18a-5p 过表达抑制 H ₂ O ₂在 HTR-8/SVneo 细胞中诱导细胞凋亡，而 miR-18a-5p 过表达对细胞凋亡的抑制作用被 LncRNA NEAT1 过表达消除。总之，LncRNA NEAT1 转录在氧化应激条件下由 p53 诱导，LncRNA NEAT1 的高表达随后通过海绵 miR-18a-5p 增加 ESRα 表达，从而诱导滋养细胞凋亡。