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Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence

The heat-sink effect and thermal damage of conventional thermal ablative technologies can be minimized by irreversible electroporation (IRE), which results in clear ablative boundaries and conservation of blood vessels, facilitating maximal safe surgical resection for glioblastoma. Although much com...

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Autores principales: Yu, Shuangquan, Chen, Lingchao, Song, Kun, Shu, Ting, Fang, Zheng, Ding, Lujia, Liu, Jilong, Jiang, Lei, Zhang, Guanqing, Zhang, Bing, Qin, Zhiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688309/
https://www.ncbi.nlm.nih.gov/pubmed/36358391
http://dx.doi.org/10.3390/brainsci12111465
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author Yu, Shuangquan
Chen, Lingchao
Song, Kun
Shu, Ting
Fang, Zheng
Ding, Lujia
Liu, Jilong
Jiang, Lei
Zhang, Guanqing
Zhang, Bing
Qin, Zhiyong
author_facet Yu, Shuangquan
Chen, Lingchao
Song, Kun
Shu, Ting
Fang, Zheng
Ding, Lujia
Liu, Jilong
Jiang, Lei
Zhang, Guanqing
Zhang, Bing
Qin, Zhiyong
author_sort Yu, Shuangquan
collection PubMed
description The heat-sink effect and thermal damage of conventional thermal ablative technologies can be minimized by irreversible electroporation (IRE), which results in clear ablative boundaries and conservation of blood vessels, facilitating maximal safe surgical resection for glioblastoma. Although much comparative data about the death forms in IRE have been published, the comprehensive genetic regulatory mechanism for apoptosis, among other forms of regulatory cell death (RCD), remains elusive. We investigated the electric field intensity threshold for apoptosis/necrosis (YO-PRO-1/PI co-staining) of the U251 human malignant glioma cell line with stepwise increased uniform field intensity. Time course samples (0–6 h) of apoptosis induction and sham treatment were collected for transcriptome sequencing. Sequencing showed that transcription factor AP-1 and its target gene Bim (Bcl2l11), related to the signaling pathway, played a major role in the apoptosis of glioma after IRE. The sequencing results were confirmed by qPCR and Western blot. We also found that the transcription changes also implicated three other forms of RCD: autophagy, necroptosis, and immunogenic cell death (ICD), in addition to apoptosis. These together imply that IRE possibly mediates apoptosis by the AP-1-Bim pathway, causes mixed RCD simultaneously, and has the potential to aid in the generation of a systemic antitumor immune response.
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spelling pubmed-96883092022-11-25 Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence Yu, Shuangquan Chen, Lingchao Song, Kun Shu, Ting Fang, Zheng Ding, Lujia Liu, Jilong Jiang, Lei Zhang, Guanqing Zhang, Bing Qin, Zhiyong Brain Sci Article The heat-sink effect and thermal damage of conventional thermal ablative technologies can be minimized by irreversible electroporation (IRE), which results in clear ablative boundaries and conservation of blood vessels, facilitating maximal safe surgical resection for glioblastoma. Although much comparative data about the death forms in IRE have been published, the comprehensive genetic regulatory mechanism for apoptosis, among other forms of regulatory cell death (RCD), remains elusive. We investigated the electric field intensity threshold for apoptosis/necrosis (YO-PRO-1/PI co-staining) of the U251 human malignant glioma cell line with stepwise increased uniform field intensity. Time course samples (0–6 h) of apoptosis induction and sham treatment were collected for transcriptome sequencing. Sequencing showed that transcription factor AP-1 and its target gene Bim (Bcl2l11), related to the signaling pathway, played a major role in the apoptosis of glioma after IRE. The sequencing results were confirmed by qPCR and Western blot. We also found that the transcription changes also implicated three other forms of RCD: autophagy, necroptosis, and immunogenic cell death (ICD), in addition to apoptosis. These together imply that IRE possibly mediates apoptosis by the AP-1-Bim pathway, causes mixed RCD simultaneously, and has the potential to aid in the generation of a systemic antitumor immune response. MDPI 2022-10-29 /pmc/articles/PMC9688309/ /pubmed/36358391 http://dx.doi.org/10.3390/brainsci12111465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Shuangquan
Chen, Lingchao
Song, Kun
Shu, Ting
Fang, Zheng
Ding, Lujia
Liu, Jilong
Jiang, Lei
Zhang, Guanqing
Zhang, Bing
Qin, Zhiyong
Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence
title Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence
title_full Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence
title_fullStr Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence
title_full_unstemmed Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence
title_short Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence
title_sort irreversible electroporation mediates glioma apoptosis via upregulation of ap-1 and bim: transcriptome evidence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688309/
https://www.ncbi.nlm.nih.gov/pubmed/36358391
http://dx.doi.org/10.3390/brainsci12111465
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