Increased miRNA-518b inhibits trophoblast migration and angiogenesis by targeting EGR1 in early embryonic arrest. Issue 4 (10th July 2019)

• Record Type: Journal Article
• Authors: Yang, Wenmei; Lu, Zhaoyi; Zhi, Zhifu; Liu, Liling; Deng, Lingjie; Jiang, Xiaoli; Pang, Lihong
• Editors: Hemberger, Myriam
• Is Part Of: Biology of reproduction. Volume 101:Issue 4(2019)
• Page Start: 664
• Page End: 674
• Publication Date: 2019-07-10
• Subjects: embryo development -- microRNA regulation -- hypoxia; Reproduction -- Periodicals; Biology; Reproduction; Reproduction; Electronic journals; Periodicals; Periodicals; 571.805
• DOI: 10.1093/biolre/ioz109
• Languages: English
• ISSNs: 0006-3363

Abstract

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. Abstract : Summary Sentence miR-518b/EGR1/VEGF plays an important role in regulating placental trophoblast migration and angiogenesis.