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Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray
BACKGROUND: Friedreich's ataxia (FRDA) is a familial hereditary disorder that lacks available therapy. Therefore, the identification of novel biomarkers and key mechanisms related to FRDA progression is urgently required. METHODS: We identified the up-regulated and down-regulated differentially...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884172/ https://www.ncbi.nlm.nih.gov/pubmed/35237223 http://dx.doi.org/10.3389/fneur.2021.816393 |
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author | Liu, Lichun Lai, Yongxing Zhan, Zhidong Fu, Qingxian Jiang, Yuelian |
author_facet | Liu, Lichun Lai, Yongxing Zhan, Zhidong Fu, Qingxian Jiang, Yuelian |
author_sort | Liu, Lichun |
collection | PubMed |
description | BACKGROUND: Friedreich's ataxia (FRDA) is a familial hereditary disorder that lacks available therapy. Therefore, the identification of novel biomarkers and key mechanisms related to FRDA progression is urgently required. METHODS: We identified the up-regulated and down-regulated differentially expressed genes (DEGs) in children and adult FRDA from the GSE11204 dataset and intersected them to determine the co-expressed DEGs (co-DEGs). Enrichment analysis was conducted and a protein-protein interaction (PPI) network was constructed to identify key pathways and hub genes. The potential diagnostic biomarkers were validated using the GSE30933 dataset. Cytoscape was applied to construct interaction and competitive endogenous RNA (ceRNA) networks. RESULTS: Gene Set Enrichment Analysis (GSEA) indicated that the genes in both the child and adult samples were primarily enriched in their immune-related functions. We identified 88 co-DEGs between child and adult FRDA samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analysis suggested that these co-DEGs were primarily enriched in immune response, inflammatory reaction, and necroptosis. Immune infiltration analysis showed remarkable differences in the proportions of immune cell subtype between FRDA and healthy samples. In addition, ten core genes and one gene cluster module were screened out based on the PPI network. We verified eight immune-specific core genes using a validation dataset and found CD28, FAS, and ITIF5 have high diagnostic significance in FRDA. Finally, NEAT1-hsa-miR-24-3p-CD28 was identified as a key regulatory pathway of child and adult FRDA. CONCLUSIONS: Downregulation of three immune-specific hub genes, CD28, FAS, and IFIT5, may be associated with the progression of child and adult FRDA. Furthermore, NEAT1-hsa-miR-24-3p-CD28 may be the potential RNA regulatory pathway related to the pathogenesis of child and adult FRDA. |
format | Online Article Text |
id | pubmed-8884172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88841722022-03-01 Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray Liu, Lichun Lai, Yongxing Zhan, Zhidong Fu, Qingxian Jiang, Yuelian Front Neurol Neurology BACKGROUND: Friedreich's ataxia (FRDA) is a familial hereditary disorder that lacks available therapy. Therefore, the identification of novel biomarkers and key mechanisms related to FRDA progression is urgently required. METHODS: We identified the up-regulated and down-regulated differentially expressed genes (DEGs) in children and adult FRDA from the GSE11204 dataset and intersected them to determine the co-expressed DEGs (co-DEGs). Enrichment analysis was conducted and a protein-protein interaction (PPI) network was constructed to identify key pathways and hub genes. The potential diagnostic biomarkers were validated using the GSE30933 dataset. Cytoscape was applied to construct interaction and competitive endogenous RNA (ceRNA) networks. RESULTS: Gene Set Enrichment Analysis (GSEA) indicated that the genes in both the child and adult samples were primarily enriched in their immune-related functions. We identified 88 co-DEGs between child and adult FRDA samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analysis suggested that these co-DEGs were primarily enriched in immune response, inflammatory reaction, and necroptosis. Immune infiltration analysis showed remarkable differences in the proportions of immune cell subtype between FRDA and healthy samples. In addition, ten core genes and one gene cluster module were screened out based on the PPI network. We verified eight immune-specific core genes using a validation dataset and found CD28, FAS, and ITIF5 have high diagnostic significance in FRDA. Finally, NEAT1-hsa-miR-24-3p-CD28 was identified as a key regulatory pathway of child and adult FRDA. CONCLUSIONS: Downregulation of three immune-specific hub genes, CD28, FAS, and IFIT5, may be associated with the progression of child and adult FRDA. Furthermore, NEAT1-hsa-miR-24-3p-CD28 may be the potential RNA regulatory pathway related to the pathogenesis of child and adult FRDA. Frontiers Media S.A. 2022-02-14 /pmc/articles/PMC8884172/ /pubmed/35237223 http://dx.doi.org/10.3389/fneur.2021.816393 Text en Copyright © 2022 Liu, Lai, Zhan, Fu and Jiang. 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 | Neurology Liu, Lichun Lai, Yongxing Zhan, Zhidong Fu, Qingxian Jiang, Yuelian Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray |
title | Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray |
title_full | Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray |
title_fullStr | Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray |
title_full_unstemmed | Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray |
title_short | Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray |
title_sort | downregulation of three immune-specific core genes and the regulatory pathways in children and adult friedreich's ataxia: a comprehensive analysis based on microarray |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884172/ https://www.ncbi.nlm.nih.gov/pubmed/35237223 http://dx.doi.org/10.3389/fneur.2021.816393 |
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