Wen Hong, Hu Ying, Chen Lu, Zhao Li, Yang Xinyun
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
Reprod Sci. 2020 Jun;27(6):1357-1364. doi: 10.1007/s43032-020-00160-3. Epub 2020 Feb 13.
Selective intrauterine growth restriction (sIUGR) is a disorder of monochorionic (MC) twin pregnancies. However, the underlying mechanism remains largely unknown. Trophoblast cells are the major component of the placenta. Dysfunction of trophoblast cells is associated with placental dysfunction. Our previous study identified miR-338-5p is downregulated in placenta tissues sharing larger twins of sIUGR. In the present study, we aimed to investigate the role of miR-338-5p in trophoblast cells and explored its target. Our results further indicated that miR-338-5p was downregulated in placental tissues supporting larger twins of sIUGR, whereas epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was upregulated. Moreover, miR-338-5p overexpression suppressed the growth and invasion of trophoblast cells. Importantly, results from luciferase reporter assay demonstrated that miR-338-5p bound on the 3'-UTR of EFEMP1. miR-338-5p suppressed the growth and invasion of trophoblast cells via targeting EFEMP1. Further, miR-338-5p/EFEMP1 might disrupt the function of trophoblast cells via inhibiting the phosphorylation of AKT.
选择性宫内生长受限(sIUGR)是单绒毛膜(MC)双胎妊娠的一种病症。然而,其潜在机制仍 largely unknown。滋养层细胞是胎盘的主要组成部分。滋养层细胞功能障碍与胎盘功能障碍相关。我们之前的研究发现,在sIUGR中较大胎儿对应的胎盘组织中miR-338-5p表达下调。在本研究中,我们旨在探究miR-338-5p在滋养层细胞中的作用并探索其靶标。我们的结果进一步表明,在支持sIUGR中较大胎儿的胎盘组织中miR-338-5p表达下调,而含表皮生长因子的纤连蛋白样细胞外基质蛋白1(EFEMP1)表达上调。此外,miR-338-5p过表达抑制了滋养层细胞的生长和侵袭。重要的是,荧光素酶报告基因检测结果表明miR-338-5p与EFEMP1的3'-UTR结合。miR-338-5p通过靶向EFEMP1抑制滋养层细胞的生长和侵袭。此外,miR-338-5p/EFEMP1可能通过抑制AKT的磷酸化来破坏滋养层细胞的功能。