Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Baicheng, Zhang, Lu, Zhou, Xinxin, Ning, Hao, Ma, Teng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784848486092505088
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
work_keys_str_mv AT zhubaicheng transcriptionfactorznf22regulatesbloodtumorbarrierpermeabilitybyinteractingwithhdac3protein
AT zhanglu transcriptionfactorznf22regulatesbloodtumorbarrierpermeabilitybyinteractingwithhdac3protein
AT zhouxinxin transcriptionfactorznf22regulatesbloodtumorbarrierpermeabilitybyinteractingwithhdac3protein
AT ninghao transcriptionfactorznf22regulatesbloodtumorbarrierpermeabilitybyinteractingwithhdac3protein
AT mateng transcriptionfactorznf22regulatesbloodtumorbarrierpermeabilitybyinteractingwithhdac3protein