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MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex
Extravillous trophoblast (EVT) invasion is required for remodeling uterine tertiary arteries and placenta development during pregnancy. Compromised EVT invasion may contribute to the pathology of placenta-related diseases. Metastasis -associated protein 3 (MTA3) is one of the subunits of nucleosome...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613952/ https://www.ncbi.nlm.nih.gov/pubmed/28959722 http://dx.doi.org/10.3934/medsci.2017.1.17 |
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author | Chen, Ying Khoo, Sok Kean Leach, Richard Wang, Kai |
author_facet | Chen, Ying Khoo, Sok Kean Leach, Richard Wang, Kai |
author_sort | Chen, Ying |
collection | PubMed |
description | Extravillous trophoblast (EVT) invasion is required for remodeling uterine tertiary arteries and placenta development during pregnancy. Compromised EVT invasion may contribute to the pathology of placenta-related diseases. Metastasis -associated protein 3 (MTA3) is one of the subunits of nucleosome remodeling and deacetylation (NuRD) complex that represses transcription in a histone deacetylase-dependent manner. MTA3 is reported to be down-regulated in preeclamptic placentas, suggesting its potential role in EVT invasion. Here, we investigate the role of MTA3 in EVT invasion by studying its molecular mechanisms in EVT cells. First, we confirmed MTA3 expression in the EVT cells in human placenta using immunohistochemistry. We then used lentivirus-mediated MTA3 short hairpin RNA (shRNA) to knock down MTA3 expression in EVT-derived HTR8/SVneo cells and found higher invasion capacity in MTA3 knockdown cells. Using quantitative real-time PCR, we showed higher expression of invasion-related genes matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and transcription factor Snail in MTA3 knockdown compared with control cells. Co-immunoprecipitation-Western blot assay showed the protein-protein interaction of histone deacetylase 1 (HDAC1), a subunit of NuRD, with MTA3 in HTR8/SVneo cells. Co-immunoprecipitation-Mass spectrometry assay further identified 71 proteins interacting with MTA3, including NuRD subunits, heterochromatin proteins, epigenetics modifiers and transcription factors. This result not only indicated the involvement of NuRD complex in MTA3’s function, but also demonstrated the complicated multiple co-players in MTA3 and NuRD complex mediated transcription repression in EVT. In summary, our data demonstrates that MTA3 regulates EVT invasion and related gene expression via NuRD complex in EVT. |
format | Online Article Text |
id | pubmed-5613952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-56139522017-09-26 MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex Chen, Ying Khoo, Sok Kean Leach, Richard Wang, Kai AIMS Med Sci Article Extravillous trophoblast (EVT) invasion is required for remodeling uterine tertiary arteries and placenta development during pregnancy. Compromised EVT invasion may contribute to the pathology of placenta-related diseases. Metastasis -associated protein 3 (MTA3) is one of the subunits of nucleosome remodeling and deacetylation (NuRD) complex that represses transcription in a histone deacetylase-dependent manner. MTA3 is reported to be down-regulated in preeclamptic placentas, suggesting its potential role in EVT invasion. Here, we investigate the role of MTA3 in EVT invasion by studying its molecular mechanisms in EVT cells. First, we confirmed MTA3 expression in the EVT cells in human placenta using immunohistochemistry. We then used lentivirus-mediated MTA3 short hairpin RNA (shRNA) to knock down MTA3 expression in EVT-derived HTR8/SVneo cells and found higher invasion capacity in MTA3 knockdown cells. Using quantitative real-time PCR, we showed higher expression of invasion-related genes matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and transcription factor Snail in MTA3 knockdown compared with control cells. Co-immunoprecipitation-Western blot assay showed the protein-protein interaction of histone deacetylase 1 (HDAC1), a subunit of NuRD, with MTA3 in HTR8/SVneo cells. Co-immunoprecipitation-Mass spectrometry assay further identified 71 proteins interacting with MTA3, including NuRD subunits, heterochromatin proteins, epigenetics modifiers and transcription factors. This result not only indicated the involvement of NuRD complex in MTA3’s function, but also demonstrated the complicated multiple co-players in MTA3 and NuRD complex mediated transcription repression in EVT. In summary, our data demonstrates that MTA3 regulates EVT invasion and related gene expression via NuRD complex in EVT. 2017-01-16 2017 /pmc/articles/PMC5613952/ /pubmed/28959722 http://dx.doi.org/10.3934/medsci.2017.1.17 Text en http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) |
spellingShingle | Article Chen, Ying Khoo, Sok Kean Leach, Richard Wang, Kai MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex |
title | MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex |
title_full | MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex |
title_fullStr | MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex |
title_full_unstemmed | MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex |
title_short | MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex |
title_sort | mta3 regulates extravillous trophoblast invasion through nurd complex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613952/ https://www.ncbi.nlm.nih.gov/pubmed/28959722 http://dx.doi.org/10.3934/medsci.2017.1.17 |
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