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微小 RNA-184 通过靶向 WIG1 促进滋养层细胞凋亡,诱导早期自然流产。

MicroRNA-184 promotes apoptosis of trophoblast cells via targeting WIG1 and induces early spontaneous abortion.

机构信息

Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, People's Republic of China.

Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, 215123, People's Republic of China.

出版信息

Cell Death Dis. 2019 Mar 4;10(3):223. doi: 10.1038/s41419-019-1443-2.

Abstract

Recurrent spontaneous abortion (RSA) refers to the unintentional termination of two or more consecutive pregnancies that severely threatens human reproductive health. Our previous study has shown that miR-184 is expressed more highly in RSA than in normal pregnancy, whether in the villus or decidua. In this study, compared with normal pregnant women, the expression of miR-184 in decidual stromal cells (DSCs) and decidual immune cells (DICs), as well as in peripheral blood, from RSA patients was enhanced similarly. Moreover, we found miR-184 could promote the apoptosis and repress the proliferation of trophoblast cells. Further exploration indicated that miR-184 upregulated the expression of Fas by targeting WIG1 thus inducing cell apoptosis. Finally, after miR-184 overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. Therefore, our study outlines the pivotal role of miR-184 in maintaining successful pregnancy, providing a new diagnostic and therapeutic target for RSA.

摘要

复发性自然流产(RSA)是指连续两次或两次以上的意外妊娠终止,严重威胁人类生殖健康。我们之前的研究表明,miR-184 在 RSA 中的表达高于正常妊娠,无论是绒毛还是蜕膜。在这项研究中,与正常孕妇相比,RSA 患者的蜕膜基质细胞(DSCs)和蜕膜免疫细胞(DICs)以及外周血中的 miR-184 表达水平相似增强。此外,我们发现 miR-184 可以通过靶向 WIG1 促进滋养细胞的凋亡和抑制增殖。进一步的探索表明,miR-184 通过靶向 WIG1 上调 Fas 的表达从而诱导细胞凋亡。最后,在体内过表达 miR-184 后,怀孕小鼠的胚胎吸收率明显增加。因此,我们的研究概述了 miR-184 在维持成功妊娠中的关键作用,为 RSA 提供了新的诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac2b/6399231/38634db898a4/41419_2019_1443_Fig1_HTML.jpg

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