Increased miRNA-518b inhibits trophoblast migration and angiogenesis by targeting EGR1 in early embryonic arrest†
Increased miRNA-518b inhibits trophoblast migration and angiogenesis by targeting EGR1 in early embryonic arrest†
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DOI：
10.1093/biolre/ioz109
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发表时间：
2019-07
影响因子：
3.6
通讯作者：
Wenmei Yang;Zhaoyi Lu;Zhifu Zhi;Liling Liu;Lingjie Deng;Xiaoli Jiang;Lihong Pang
中科院分区：
文献类型：
--
作者：
Wenmei Yang;Zhaoyi Lu;Zhifu Zhi;Liling Liu;Lingjie Deng;Xiaoli Jiang;Lihong Pang
摘要有证据表明microRNAs（miRNAs）在早期胚胎发育中起着重要作用。miRNA-518家族是胎盘的一种特殊生物标志物，miRNA-518 b在子痫前期胎盘组织中异常表达。早期生长反应蛋白1（EGR 1）是一种锌指转录因子，在调节细胞分化、血管生成和迁移中起重要作用。此外，早期的研究表明，EGR 1蛋白在植入中起着关键作用。然而，关于miR-518 b和EGFR 1在人类早期胚胎停滞（EEA）中的作用知之甚少。在我们的研究中，在EEA的人绒毛组织中发现miR-518 b沿着EGFR 1的减少而增加。此外，我们通过荧光素酶测定证明miR-518 b是EGFR 1的直接调节剂。在比较单独沉默EGR 1、血管内皮生长因子（VEGF）以及EGR 1/VEGF联合沉默的效果后，我们发现EGR 1可以通过降低VEGF的表达来抑制HTR-8 SVneo细胞的迁移和血管生成。缺氧在早期胚胎发育中起着初始作用，我们发现缺氧降低了miR-518 b的表达，并增加了EGFR 1和VEGF的表达，以促进HTR-8/SVneo细胞系缺氧模型中的迁移和血管生成。我们的研究结果为miR-518 b在EEA中的作用提供了新的见解，并暗示miR-518 b在EEA的诊断和干预发展中的潜在应用。miR-518 b/EGR 1/VEGF在调节胎盘滋养层细胞迁移和血管生成中起重要作用。
Abstract Evidence indicates that microRNAs (miRNAs) play essential roles in early embryonic development. The miRNA-518 family is a special biomarker of the placenta, and miRNA-518b is abnormally expressed in placental tissue in preeclampsia. Early growth response protein 1 (EGR1), a zinc finger transcriptional factor, plays an essential role in regulating cell differentiation, angiogenesis, and migration. Moreover, earlier studies have shown that EGR1 protein plays a key role in implantation. However, little is known about the role of miR-518b and EGR1 on early embryonic arrest (EEA) in humans. In our study, increased miR-518b along with decreased EGR1 was found in human villus tissues with EEA. Furthermore, we demonstrated by luciferase assay that miR-518b is a direct regulator of EGR1. After comparing the effect of silencing EGR1, vascular endothelial growth factor (VEGF) individually, and EGR1/VEGF in combination, we found that EGR1 can inhibit migration and angiogenesis of HTR-8 SVneo cells by decreasing the VEGF expression. Hypoxia plays an initial role in early embryonic development, and we found that hypoxia reduces the expression of miR-518b and increases the expression of EGR1 and VEGF to facilitate migration and angiogenesis in a hypoxic model of HTR-8/SVneo cell line. Our findings provide new insights into the role of miR-518b in EEA and implicate the potential application of miR-518b in the diagnosis and development of intervention for EEA. Summary Sentence miR-518b/EGR1/VEGF plays an important role in regulating placental trophoblast migration and angiogenesis.