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Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant form of glioma and represents 81% of malignant brain and central nervous system (CNS) tumors. Like most cancers, GBM causes metabolic recombination to promote cell survival, proliferation, and invasion of cancer cells....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533644/ https://www.ncbi.nlm.nih.gov/pubmed/33072547 http://dx.doi.org/10.3389/fonc.2020.01549 |
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author | Han, Xudong Wang, Donghua Zhao, Ping Liu, Chonghui Hao, Yue Chang, Lulu Zhao, Jiarui Zhao, Wei Mu, Lili Wang, Jinghua Li, Hulun Kong, Qingfei Han, Junwei |
author_facet | Han, Xudong Wang, Donghua Zhao, Ping Liu, Chonghui Hao, Yue Chang, Lulu Zhao, Jiarui Zhao, Wei Mu, Lili Wang, Jinghua Li, Hulun Kong, Qingfei Han, Junwei |
author_sort | Han, Xudong |
collection | PubMed |
description | Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant form of glioma and represents 81% of malignant brain and central nervous system (CNS) tumors. Like most cancers, GBM causes metabolic recombination to promote cell survival, proliferation, and invasion of cancer cells. In this study, we propose a method for constructing the metabolic subpathway activity score matrix to accurately identify abnormal targets of GBM metabolism. By integrating gene expression data from different sequencing methods, our method identified 25 metabolic subpathways that were significantly abnormal in the GBM patient population, and most of these subpathways have been reported to have an effect on GBM. Through the analysis of 25 GBM-related metabolic subpathways, we found that (S)-2,3-Epoxysqualene, which was at the central region of the sterol biosynthesis subpathway, may have a greater impact on the entire pathway, suggesting a potential high association with GBM. Analysis of CCK8 cell activity indicated that (S)-2,3-Epoxysqualene can indeed inhibit the activity of U87-MG cells. By flow cytometry, we demonstrated that (S)-2,3-Epoxysqualene not only arrested the U87-MG cell cycle in the G0/G1 phase but also induced cell apoptosis. These results confirm the reliability of our proposed metabolic subpathway identification method and suggest that (S)-2,3-Epoxysqualene has potential therapeutic value for GBM. In order to make the method more broadly applicable, we have developed an R system package crmSubpathway to perform disease-related metabolic subpathway identification and it is freely available on the GitHub (https://github.com/hanjunwei-lab/crmSubpathway). |
format | Online Article Text |
id | pubmed-7533644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75336442020-10-15 Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme Han, Xudong Wang, Donghua Zhao, Ping Liu, Chonghui Hao, Yue Chang, Lulu Zhao, Jiarui Zhao, Wei Mu, Lili Wang, Jinghua Li, Hulun Kong, Qingfei Han, Junwei Front Oncol Oncology Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant form of glioma and represents 81% of malignant brain and central nervous system (CNS) tumors. Like most cancers, GBM causes metabolic recombination to promote cell survival, proliferation, and invasion of cancer cells. In this study, we propose a method for constructing the metabolic subpathway activity score matrix to accurately identify abnormal targets of GBM metabolism. By integrating gene expression data from different sequencing methods, our method identified 25 metabolic subpathways that were significantly abnormal in the GBM patient population, and most of these subpathways have been reported to have an effect on GBM. Through the analysis of 25 GBM-related metabolic subpathways, we found that (S)-2,3-Epoxysqualene, which was at the central region of the sterol biosynthesis subpathway, may have a greater impact on the entire pathway, suggesting a potential high association with GBM. Analysis of CCK8 cell activity indicated that (S)-2,3-Epoxysqualene can indeed inhibit the activity of U87-MG cells. By flow cytometry, we demonstrated that (S)-2,3-Epoxysqualene not only arrested the U87-MG cell cycle in the G0/G1 phase but also induced cell apoptosis. These results confirm the reliability of our proposed metabolic subpathway identification method and suggest that (S)-2,3-Epoxysqualene has potential therapeutic value for GBM. In order to make the method more broadly applicable, we have developed an R system package crmSubpathway to perform disease-related metabolic subpathway identification and it is freely available on the GitHub (https://github.com/hanjunwei-lab/crmSubpathway). Frontiers Media S.A. 2020-09-11 /pmc/articles/PMC7533644/ /pubmed/33072547 http://dx.doi.org/10.3389/fonc.2020.01549 Text en Copyright © 2020 Han, Wang, Zhao, Liu, Hao, Chang, Zhao, Zhao, Mu, Wang, Li, Kong and Han. http://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 | Oncology Han, Xudong Wang, Donghua Zhao, Ping Liu, Chonghui Hao, Yue Chang, Lulu Zhao, Jiarui Zhao, Wei Mu, Lili Wang, Jinghua Li, Hulun Kong, Qingfei Han, Junwei Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme |
title | Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme |
title_full | Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme |
title_fullStr | Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme |
title_full_unstemmed | Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme |
title_short | Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme |
title_sort | inference of subpathway activity profiles reveals metabolism abnormal subpathway regions in glioblastoma multiforme |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533644/ https://www.ncbi.nlm.nih.gov/pubmed/33072547 http://dx.doi.org/10.3389/fonc.2020.01549 |
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