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Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity

Epilepsy, a functional disease caused by abnormal discharge of neurons, has attracted the attention of neurologists due to its complex characteristics. N6-methyladenosine (m6A) is a reversible mRNA modification that plays essential role in various biological processes. Nevertheless, no previous stud...

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Autores principales: Liu, Xuchen, Sun, Qingyuan, Cao, Zexin, Liu, Wenyu, Zhang, Hengrui, Xue, Zhiwei, Zhao, Jiangli, Feng, Yifei, Zhao, Feihu, Wang, Jiwei, Wang, Xinyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714553/
https://www.ncbi.nlm.nih.gov/pubmed/36468034
http://dx.doi.org/10.3389/fgene.2022.1042543
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author Liu, Xuchen
Sun, Qingyuan
Cao, Zexin
Liu, Wenyu
Zhang, Hengrui
Xue, Zhiwei
Zhao, Jiangli
Feng, Yifei
Zhao, Feihu
Wang, Jiwei
Wang, Xinyu
author_facet Liu, Xuchen
Sun, Qingyuan
Cao, Zexin
Liu, Wenyu
Zhang, Hengrui
Xue, Zhiwei
Zhao, Jiangli
Feng, Yifei
Zhao, Feihu
Wang, Jiwei
Wang, Xinyu
author_sort Liu, Xuchen
collection PubMed
description Epilepsy, a functional disease caused by abnormal discharge of neurons, has attracted the attention of neurologists due to its complex characteristics. N6-methyladenosine (m6A) is a reversible mRNA modification that plays essential role in various biological processes. Nevertheless, no previous study has systematically evaluated the role of m6A regulators in epilepsy. Here, using gene expression screening in the Gene Expression Omnibus GSE143272, we identified seven significant m6A regulator genes in epileptic and non-epileptic patients. The random forest (RF) model was applied to the screening, and seven m6A regulators (HNRNPC, WATP, RBM15, YTHDC1, YTHDC2, CBLL1, and RBMX) were selected as the candidate genes for predicting the risk of epilepsy. A nomogram model was then established based on the seven-candidate m6A regulators. Decision curve analysis preliminarily showed that patients with epilepsy could benefit from the nomogram model. The consensus clustering method was performed to divide patients with epilepsy into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, the patients in each cluster had unique immune cell components and different cell death patterns. Meanwhile, based on the M6A classification, a correlation between epilepsy and glucose metabolism was laterally verified. In conclusion, the m6A regulation pattern plays a vital role in the pathogenesis of epilepsy. The research on m6A regulatory factors will play a key role in guiding the immune-related treatment, drug selection, and identification of metabolism conditions and mechanisms of epilepsy in the future.
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spelling pubmed-97145532022-12-02 Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity Liu, Xuchen Sun, Qingyuan Cao, Zexin Liu, Wenyu Zhang, Hengrui Xue, Zhiwei Zhao, Jiangli Feng, Yifei Zhao, Feihu Wang, Jiwei Wang, Xinyu Front Genet Genetics Epilepsy, a functional disease caused by abnormal discharge of neurons, has attracted the attention of neurologists due to its complex characteristics. N6-methyladenosine (m6A) is a reversible mRNA modification that plays essential role in various biological processes. Nevertheless, no previous study has systematically evaluated the role of m6A regulators in epilepsy. Here, using gene expression screening in the Gene Expression Omnibus GSE143272, we identified seven significant m6A regulator genes in epileptic and non-epileptic patients. The random forest (RF) model was applied to the screening, and seven m6A regulators (HNRNPC, WATP, RBM15, YTHDC1, YTHDC2, CBLL1, and RBMX) were selected as the candidate genes for predicting the risk of epilepsy. A nomogram model was then established based on the seven-candidate m6A regulators. Decision curve analysis preliminarily showed that patients with epilepsy could benefit from the nomogram model. The consensus clustering method was performed to divide patients with epilepsy into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, the patients in each cluster had unique immune cell components and different cell death patterns. Meanwhile, based on the M6A classification, a correlation between epilepsy and glucose metabolism was laterally verified. In conclusion, the m6A regulation pattern plays a vital role in the pathogenesis of epilepsy. The research on m6A regulatory factors will play a key role in guiding the immune-related treatment, drug selection, and identification of metabolism conditions and mechanisms of epilepsy in the future. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9714553/ /pubmed/36468034 http://dx.doi.org/10.3389/fgene.2022.1042543 Text en Copyright © 2022 Liu, Sun, Cao, Liu, Zhang, Xue, Zhao, Feng, Zhao, Wang and Wang. 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 Genetics
Liu, Xuchen
Sun, Qingyuan
Cao, Zexin
Liu, Wenyu
Zhang, Hengrui
Xue, Zhiwei
Zhao, Jiangli
Feng, Yifei
Zhao, Feihu
Wang, Jiwei
Wang, Xinyu
Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
title Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
title_full Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
title_fullStr Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
title_full_unstemmed Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
title_short Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
title_sort identification of rna n6-methyladenosine regulation in epilepsy: significance of the cell death mode, glycometabolism, and drug reactivity
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714553/
https://www.ncbi.nlm.nih.gov/pubmed/36468034
http://dx.doi.org/10.3389/fgene.2022.1042543
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