Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784842253930332160 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9714553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liuxuchen identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT sunqingyuan identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT caozexin identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT liuwenyu identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT zhanghengrui identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT xuezhiwei identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT zhaojiangli identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT fengyifei identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT zhaofeihu identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT wangjiwei identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity AT wangxinyu identificationofrnan6methyladenosineregulationinepilepsysignificanceofthecelldeathmodeglycometabolismanddrugreactivity |