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长链非编码 RNA LINC01088 抑制滋养细胞功能,激活 MAPK 信号通路,并与复发性妊娠丢失相关。

LncRNA LINC01088 inhibits the function of trophoblast cells, activates the MAPK-signaling pathway and associates with recurrent pregnancy loss.

机构信息

Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

Department of Obstetrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

出版信息

Mol Hum Reprod. 2021 Aug 7;27(8). doi: 10.1093/molehr/gaab047.

Abstract

Long noncoding RNAs (lncRNAs) have been reported to be involved in various cellular processes and to participate in a variety of human diseases. Recently, increasing studies have reported that lncRNAs are related to many reproductive diseases, such as pathogenesis of recurrent pregnancy loss (RPL), preeclampsia (PE) and gestational diabetes mellitus (GDM). In this study, we aimed to investigate the effect of LINC01088 in trophoblast cells and its potential role in pathogenesis of RPL. LINC01088 was found to be upregulated in first-trimester chorionic villi tissues from RPL patients. Increased LINC01088 repressed proliferation, migration and invasion of trophoblast cells, and promoted apoptosis of trophoblast cells. Further exploration indicated that LINC01088 decreased the production of nitric oxide (NO) by binding and increasing Arginase-1 and decreasing eNOS protein levels. Importantly, JNK and p38 MAPK-signaling pathways were active after overexpression of LINC01088. In conclusion, our studies demonstrated that LINC01088 plays an important role in the pathogenesis of RPL, and is a potential therapeutic target for the treatment of RPL.

摘要

长链非编码 RNA(lncRNAs)已被报道参与多种细胞过程,并参与多种人类疾病。最近,越来越多的研究表明,lncRNAs 与许多生殖疾病有关,如复发性妊娠丢失(RPL)、子痫前期(PE)和妊娠期糖尿病(GDM)的发病机制。在这项研究中,我们旨在研究 LINC01088 在滋养细胞中的作用及其在 RPL 发病机制中的潜在作用。研究发现,LINC01088 在 RPL 患者的早期绒毛组织中上调。增加的 LINC01088 抑制滋养细胞的增殖、迁移和侵袭,并促进滋养细胞的凋亡。进一步探索表明,LINC01088 通过结合并增加精氨酸酶 1(Arginase-1)和减少 eNOS 蛋白水平来降低一氧化氮(NO)的产生。重要的是,LINC01088 的过表达后 JNK 和 p38 MAPK 信号通路被激活。总之,我们的研究表明,LINC01088 在 RPL 的发病机制中起重要作用,是治疗 RPL 的潜在治疗靶点。

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