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Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein
OBJECTIVE: The primary goals of this study were to investigate the potential roles of ZNF22 and HDAC3 as a histone deacetylase in regulating an increases in blood-tumor barrier (BTB) permeability and some of the possible molecular mechanisms associated with this effect. METHODS: The expression of ZN...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742255/ https://www.ncbi.nlm.nih.gov/pubmed/36518188 http://dx.doi.org/10.3389/fnmol.2022.1027942 |
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author | Zhu, Baicheng Zhang, Lu Zhou, Xinxin Ning, Hao Ma, Teng |
author_facet | Zhu, Baicheng Zhang, Lu Zhou, Xinxin Ning, Hao Ma, Teng |
author_sort | Zhu, Baicheng |
collection | PubMed |
description | OBJECTIVE: The primary goals of this study were to investigate the potential roles of ZNF22 and HDAC3 as a histone deacetylase in regulating an increases in blood-tumor barrier (BTB) permeability and some of the possible molecular mechanisms associated with this effect. METHODS: The expression of ZNF22 and HDAC3 in glioma-exposed endothelial cells (GECs) of BTB were detected transcription real-time PCR or western blot. The interaction of ZNF22 and HDAC3 in GECs associated with transcript effect was analyzed by means of Co-Immunoprecipitation and luciferase reporter assay. RESULTS: In the present investigation, GECs expressed higher levels of ZNF22 as a zinc finger transcription factor and HDAC3 than endothelial cells. We then affirmed that silencing HDAC3 or ZNF22 led to a reduction in BTB permeability. By bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and luciferase assay, we found that ZNF22 had a target binding relationship with the promoter regions of ZO-1, Occludin, and Claudin-5 and negatively regulated the expression of ZO-1, Occludin, and Claudin-5. Furthermore, we revealed that HDAC3, as a co-transcript repressor with histone deacetylase activity, could interact with ZNF22 to hinder the expression of TJ-associated proteins, thereby further facilitating the permeability of BTB. CONCLUSION: ZNF22 acted as a transcription factor in conjunction with HDAC3 to modulate the expression of TJ-associated proteins, which was correlated with an increase in BTB permeability. These results may provide new strategies and targets for the chemotherapy of gliomas as well as intracranial infections. |
format | Online Article Text |
id | pubmed-9742255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97422552022-12-13 Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein Zhu, Baicheng Zhang, Lu Zhou, Xinxin Ning, Hao Ma, Teng Front Mol Neurosci Neuroscience OBJECTIVE: The primary goals of this study were to investigate the potential roles of ZNF22 and HDAC3 as a histone deacetylase in regulating an increases in blood-tumor barrier (BTB) permeability and some of the possible molecular mechanisms associated with this effect. METHODS: The expression of ZNF22 and HDAC3 in glioma-exposed endothelial cells (GECs) of BTB were detected transcription real-time PCR or western blot. The interaction of ZNF22 and HDAC3 in GECs associated with transcript effect was analyzed by means of Co-Immunoprecipitation and luciferase reporter assay. RESULTS: In the present investigation, GECs expressed higher levels of ZNF22 as a zinc finger transcription factor and HDAC3 than endothelial cells. We then affirmed that silencing HDAC3 or ZNF22 led to a reduction in BTB permeability. By bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and luciferase assay, we found that ZNF22 had a target binding relationship with the promoter regions of ZO-1, Occludin, and Claudin-5 and negatively regulated the expression of ZO-1, Occludin, and Claudin-5. Furthermore, we revealed that HDAC3, as a co-transcript repressor with histone deacetylase activity, could interact with ZNF22 to hinder the expression of TJ-associated proteins, thereby further facilitating the permeability of BTB. CONCLUSION: ZNF22 acted as a transcription factor in conjunction with HDAC3 to modulate the expression of TJ-associated proteins, which was correlated with an increase in BTB permeability. These results may provide new strategies and targets for the chemotherapy of gliomas as well as intracranial infections. Frontiers Media S.A. 2022-11-28 /pmc/articles/PMC9742255/ /pubmed/36518188 http://dx.doi.org/10.3389/fnmol.2022.1027942 Text en Copyright © 2022 Zhu, Zhang, Zhou, Ning and Ma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Zhu, Baicheng Zhang, Lu Zhou, Xinxin Ning, Hao Ma, Teng Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein |
title | Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein |
title_full | Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein |
title_fullStr | Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein |
title_full_unstemmed | Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein |
title_short | Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein |
title_sort | transcription factor znf22 regulates blood-tumor barrier permeability by interacting with hdac3 protein |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742255/ https://www.ncbi.nlm.nih.gov/pubmed/36518188 http://dx.doi.org/10.3389/fnmol.2022.1027942 |
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