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Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma
m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator–target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to ex...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473691/ https://www.ncbi.nlm.nih.gov/pubmed/34589481 http://dx.doi.org/10.3389/fcell.2021.709022 |
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author | Cong, Peilin Wu, Tingmei Huang, Xinwei Liang, Huazheng Gao, Xiaofei Tian, Li Li, Wanrong Chen, Aiwen Wan, Hanxi He, Mengfan Dai, Danqing Li, Zhen Xiong, Lize |
author_facet | Cong, Peilin Wu, Tingmei Huang, Xinwei Liang, Huazheng Gao, Xiaofei Tian, Li Li, Wanrong Chen, Aiwen Wan, Hanxi He, Mengfan Dai, Danqing Li, Zhen Xiong, Lize |
author_sort | Cong, Peilin |
collection | PubMed |
description | m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator–target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to explore the role and prognostic value of m6A RNA methylation regulators and their targets. Expression profiles and clinicopathological data were obtained from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteome Tumor Analysis Consortium (CPTAC) datasets. Differential expression and correlation analyses were performed between normal and glioma tissues at mRNA and protein levels. Univariate Cox regression, survival, and Lasso Cox regression analyses were conducted to identify and establish the prognostic gene signature. Kaplan–Meier curve, multivariate Cox regression analysis, and ROC were utilized to evaluate the prognostic capacity of the prognostic gene signature. The correlation analysis, systematic bioinformatics analysis, and cell experiment were performed to further understand the potential underlying molecular mechanisms and drug sensitivity. Our results suggested that IGF2BP2, KIAA1429, METTL16, and METTL3, as well as 208 targets are involved in the occurrence of glioma, GBM, and LGG. YTHDF1 and 78 targets involved the occurrence of glioma and GBM, not LGG, among which 181 genes were associated with overall survival. From other findings and our cell experiment results, we demonstrated that METTL3 can activate Notch pathway and facilitate glioma occurrence through regulating its direct targets NOTCH3, DLL3, and HES1, and Notch pathway genes may serve as the potential treatment targets for glioma. Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development. |
format | Online Article Text |
id | pubmed-8473691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84736912021-09-28 Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma Cong, Peilin Wu, Tingmei Huang, Xinwei Liang, Huazheng Gao, Xiaofei Tian, Li Li, Wanrong Chen, Aiwen Wan, Hanxi He, Mengfan Dai, Danqing Li, Zhen Xiong, Lize Front Cell Dev Biol Cell and Developmental Biology m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator–target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to explore the role and prognostic value of m6A RNA methylation regulators and their targets. Expression profiles and clinicopathological data were obtained from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteome Tumor Analysis Consortium (CPTAC) datasets. Differential expression and correlation analyses were performed between normal and glioma tissues at mRNA and protein levels. Univariate Cox regression, survival, and Lasso Cox regression analyses were conducted to identify and establish the prognostic gene signature. Kaplan–Meier curve, multivariate Cox regression analysis, and ROC were utilized to evaluate the prognostic capacity of the prognostic gene signature. The correlation analysis, systematic bioinformatics analysis, and cell experiment were performed to further understand the potential underlying molecular mechanisms and drug sensitivity. Our results suggested that IGF2BP2, KIAA1429, METTL16, and METTL3, as well as 208 targets are involved in the occurrence of glioma, GBM, and LGG. YTHDF1 and 78 targets involved the occurrence of glioma and GBM, not LGG, among which 181 genes were associated with overall survival. From other findings and our cell experiment results, we demonstrated that METTL3 can activate Notch pathway and facilitate glioma occurrence through regulating its direct targets NOTCH3, DLL3, and HES1, and Notch pathway genes may serve as the potential treatment targets for glioma. Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development. Frontiers Media S.A. 2021-09-13 /pmc/articles/PMC8473691/ /pubmed/34589481 http://dx.doi.org/10.3389/fcell.2021.709022 Text en Copyright © 2021 Cong, Wu, Huang, Liang, Gao, Tian, Li, Chen, Wan, He, Dai, Li and Xiong. 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 | Cell and Developmental Biology Cong, Peilin Wu, Tingmei Huang, Xinwei Liang, Huazheng Gao, Xiaofei Tian, Li Li, Wanrong Chen, Aiwen Wan, Hanxi He, Mengfan Dai, Danqing Li, Zhen Xiong, Lize Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma |
title | Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma |
title_full | Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma |
title_fullStr | Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma |
title_full_unstemmed | Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma |
title_short | Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma |
title_sort | identification of the role and clinical prognostic value of target genes of m6a rna methylation regulators in glioma |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473691/ https://www.ncbi.nlm.nih.gov/pubmed/34589481 http://dx.doi.org/10.3389/fcell.2021.709022 |
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