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EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway

Trophoblast dysfunction is one mechanism implicated in the etiology of recurrent miscarriage (RM). Regulation of trophoblast function, however, is complex and the mechanisms contributing to dysregulation remain to be elucidated. Herein, we found EIF5A1 expression levels to be significantly decreased...

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Autores principales: Zhang, Jing, Mo, Hui-Qin, Tian, Fu-Ju, Zeng, Wei-Hong, Liu, Xiao-Rui, Ma, Xiao-Ling, Li, Xiao, Qin, Shi, Fan, Cui-Fang, Lin, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134074/
https://www.ncbi.nlm.nih.gov/pubmed/30206208
http://dx.doi.org/10.1038/s41419-018-0971-5
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author Zhang, Jing
Mo, Hui-Qin
Tian, Fu-Ju
Zeng, Wei-Hong
Liu, Xiao-Rui
Ma, Xiao-Ling
Li, Xiao
Qin, Shi
Fan, Cui-Fang
Lin, Yi
author_facet Zhang, Jing
Mo, Hui-Qin
Tian, Fu-Ju
Zeng, Wei-Hong
Liu, Xiao-Rui
Ma, Xiao-Ling
Li, Xiao
Qin, Shi
Fan, Cui-Fang
Lin, Yi
author_sort Zhang, Jing
collection PubMed
description Trophoblast dysfunction is one mechanism implicated in the etiology of recurrent miscarriage (RM). Regulation of trophoblast function, however, is complex and the mechanisms contributing to dysregulation remain to be elucidated. Herein, we found EIF5A1 expression levels to be significantly decreased in cytotrophoblasts in RM villous tissues compared with healthy controls. Using the HTR-8/SVneo cell line as a model system, we found that overexpression of EIF5A1 promotes trophoblast proliferation, migration and invasion in vitro. Knockdown of EIF5A1 or inhibiting its hypusination with N1-guanyl-1,7-diaminoheptane (GC7) suppresses these activities. Similarly, mutating EIF5A1 to EIF5A1(K50A) to prevent hypusination abolishes its effects on proliferation, migration and invasion. Furthermore, upregulation of EIF5A1 increases the outgrowth of trophoblasts in a villous explant culture model, whereas knockdown has the opposite effect. Suppression of EIF5A1 hypusination also inhibits the outgrowth of trophoblasts in explants. Mechanistically, ARAF mediates the regulation of trophoblast migration and invasion by EIF5A1. Hypusinated EIF5A1 regulates the integrin/ERK signaling pathway via controlling the translation of ARAF. ARAF level is also downregulated in trophoblasts of RM villous tissues and expression of ARAF is positively correlated with EIF5A1. Together, our results suggest that EIF5A1 may be a regulator of trophoblast function at the maternal–fetal interface and low levels of EIF5A1 and ARAF may be associated with RM.
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spelling pubmed-61340742018-09-13 EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway Zhang, Jing Mo, Hui-Qin Tian, Fu-Ju Zeng, Wei-Hong Liu, Xiao-Rui Ma, Xiao-Ling Li, Xiao Qin, Shi Fan, Cui-Fang Lin, Yi Cell Death Dis Article Trophoblast dysfunction is one mechanism implicated in the etiology of recurrent miscarriage (RM). Regulation of trophoblast function, however, is complex and the mechanisms contributing to dysregulation remain to be elucidated. Herein, we found EIF5A1 expression levels to be significantly decreased in cytotrophoblasts in RM villous tissues compared with healthy controls. Using the HTR-8/SVneo cell line as a model system, we found that overexpression of EIF5A1 promotes trophoblast proliferation, migration and invasion in vitro. Knockdown of EIF5A1 or inhibiting its hypusination with N1-guanyl-1,7-diaminoheptane (GC7) suppresses these activities. Similarly, mutating EIF5A1 to EIF5A1(K50A) to prevent hypusination abolishes its effects on proliferation, migration and invasion. Furthermore, upregulation of EIF5A1 increases the outgrowth of trophoblasts in a villous explant culture model, whereas knockdown has the opposite effect. Suppression of EIF5A1 hypusination also inhibits the outgrowth of trophoblasts in explants. Mechanistically, ARAF mediates the regulation of trophoblast migration and invasion by EIF5A1. Hypusinated EIF5A1 regulates the integrin/ERK signaling pathway via controlling the translation of ARAF. ARAF level is also downregulated in trophoblasts of RM villous tissues and expression of ARAF is positively correlated with EIF5A1. Together, our results suggest that EIF5A1 may be a regulator of trophoblast function at the maternal–fetal interface and low levels of EIF5A1 and ARAF may be associated with RM. Nature Publishing Group UK 2018-09-11 /pmc/articles/PMC6134074/ /pubmed/30206208 http://dx.doi.org/10.1038/s41419-018-0971-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Jing
Mo, Hui-Qin
Tian, Fu-Ju
Zeng, Wei-Hong
Liu, Xiao-Rui
Ma, Xiao-Ling
Li, Xiao
Qin, Shi
Fan, Cui-Fang
Lin, Yi
EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
title EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
title_full EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
title_fullStr EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
title_full_unstemmed EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
title_short EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway
title_sort eif5a1 promotes trophoblast migration and invasion via araf-mediated activation of the integrin/erk signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134074/
https://www.ncbi.nlm.nih.gov/pubmed/30206208
http://dx.doi.org/10.1038/s41419-018-0971-5
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