Department of Obstetrics and Gynecology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Free Radic Res. 2020 Sep;54(8-9):678-686. doi: 10.1080/10715762.2020.1826468. Epub 2020 Oct 1.
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 HO-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 HO-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.
胎盘氧化应激诱导的滋养细胞凋亡是子痫前期（PE）病理发展的一个因素，但其分子机制尚不清楚。在这项研究中，我们探讨了长非编码 RNA（LncRNA）NEAT1 在滋养细胞凋亡中的作用和机制。在 PE 患者的胎盘组织和 HO 处理的人滋养细胞系 HTR-8/SVneo 中，LncRNA NEAT1、p53 和雌激素受体α（ESRα）的表达增加，而 miR-18a-5p 的表达减少。LncRNA NEAT1 的过表达上调了 HTR-8/SVneo 细胞中的 ESRα 表达，而 miR-18a-5p 的过表达下调了 ESRα 表达。LncRNA NEAT1 可以通过海绵吸附 miR-18a-5p 释放 ESRα 表达，并且 p53 促进了 LncRNA NEAT1 的转录。miR-18a-5p 的过表达抑制了 HTR-8/SVneo 细胞中 HO 诱导的细胞凋亡，而 LncRNA NEAT1 的过表达消除了 miR-18a-5p 过表达对细胞凋亡的抑制作用。总之，在氧化应激条件下，p53 诱导 LncRNA NEAT1 的转录，高表达的 LncRNA NEAT1 随后通过海绵吸附 miR-18a-5p 增加 ESRα 表达，从而诱导滋养细胞凋亡。
