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Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses

BACKGROUND: Immune cells play an integral role in the development and progression of non-alcoholic fatty liver disease (NAFLD). This study was to identify immune-cell-related biomarkers for the diagnosis and treatment of NAFLD. METHODS AND FINDINGS: First, we introduced human liver transcriptome dat...

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Autores principales: Li, Gerui, Li, Hang, Chen, Ze
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235545/
https://www.ncbi.nlm.nih.gov/pubmed/37274336
http://dx.doi.org/10.3389/fendo.2023.1161269
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author Li, Gerui
Li, Hang
Chen, Ze
author_facet Li, Gerui
Li, Hang
Chen, Ze
author_sort Li, Gerui
collection PubMed
description BACKGROUND: Immune cells play an integral role in the development and progression of non-alcoholic fatty liver disease (NAFLD). This study was to identify immune-cell-related biomarkers for the diagnosis and treatment of NAFLD. METHODS AND FINDINGS: First, we introduced human liver transcriptome data from the GEO database (GSE48452 and GSE126848) and performed a weighted gene co-expression network analysis (WGCNA) to screen out the modules related to immune cell infiltration and to identify immune-cell-related differentially expressed genes (ICR-DEGs) associated with NAFLD progression. Further, the protein-protein interaction (PPI) network of ICR-DEGs was established to obtain hub genes and subsequently, the expression trend analysis was conducted to identify immune-cell-related biomarkers of NAFLD. Finally, the mRNA expression of biomarkers was validated in a NAFLD mouse model induced by high-fat diet (HFD) feeding. In total, we identified 66 ICR-DEGs and 13 hub genes associated with NAFLD. Among them, 9 hub genes (CD247, CD74, FCGR2B, IL2RB, INPP5D, MRPL16, RPL35, RPS3A, RPS8) were correlated with the infiltrating immune cells by the Pearson correlation analysis. Subsequently, 4 immune-cell-related biomarkers (RPL35, RPS3A, RPS8, and MRPL16) with the same expression trends in GSE48452 and GSE126848 datasets were identified. These biomarkers were enriched in immune-related pathways and had a good ability to distinguish between NASH and healthy samples. Moreover, we constructed a competing endogenous RNA (ceRNA) network of biomarkers and predicted twenty potential therapeutic drugs targeting RPS3A such as taxifolin and sitagliptin. Finally, experimental validation indicated that the hepatic mRNA expression of Rpl35, Rps3A, and Rps8 was significantly decreased in NAFLD mice. CONCLUSIONS: This study identified four ribosomal protein genes (RPL35, RPS3A, RPS8, and MRPL16) as immune-cell-related biomarkers of NAFLD, which may actively participate in the immune processes during NAFLD progression and could serve as potential targets for the diagnosis and treatment of NAFLD.
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spelling pubmed-102355452023-06-03 Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses Li, Gerui Li, Hang Chen, Ze Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Immune cells play an integral role in the development and progression of non-alcoholic fatty liver disease (NAFLD). This study was to identify immune-cell-related biomarkers for the diagnosis and treatment of NAFLD. METHODS AND FINDINGS: First, we introduced human liver transcriptome data from the GEO database (GSE48452 and GSE126848) and performed a weighted gene co-expression network analysis (WGCNA) to screen out the modules related to immune cell infiltration and to identify immune-cell-related differentially expressed genes (ICR-DEGs) associated with NAFLD progression. Further, the protein-protein interaction (PPI) network of ICR-DEGs was established to obtain hub genes and subsequently, the expression trend analysis was conducted to identify immune-cell-related biomarkers of NAFLD. Finally, the mRNA expression of biomarkers was validated in a NAFLD mouse model induced by high-fat diet (HFD) feeding. In total, we identified 66 ICR-DEGs and 13 hub genes associated with NAFLD. Among them, 9 hub genes (CD247, CD74, FCGR2B, IL2RB, INPP5D, MRPL16, RPL35, RPS3A, RPS8) were correlated with the infiltrating immune cells by the Pearson correlation analysis. Subsequently, 4 immune-cell-related biomarkers (RPL35, RPS3A, RPS8, and MRPL16) with the same expression trends in GSE48452 and GSE126848 datasets were identified. These biomarkers were enriched in immune-related pathways and had a good ability to distinguish between NASH and healthy samples. Moreover, we constructed a competing endogenous RNA (ceRNA) network of biomarkers and predicted twenty potential therapeutic drugs targeting RPS3A such as taxifolin and sitagliptin. Finally, experimental validation indicated that the hepatic mRNA expression of Rpl35, Rps3A, and Rps8 was significantly decreased in NAFLD mice. CONCLUSIONS: This study identified four ribosomal protein genes (RPL35, RPS3A, RPS8, and MRPL16) as immune-cell-related biomarkers of NAFLD, which may actively participate in the immune processes during NAFLD progression and could serve as potential targets for the diagnosis and treatment of NAFLD. Frontiers Media S.A. 2023-05-19 /pmc/articles/PMC10235545/ /pubmed/37274336 http://dx.doi.org/10.3389/fendo.2023.1161269 Text en Copyright © 2023 Li, Li and Chen 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 Endocrinology
Li, Gerui
Li, Hang
Chen, Ze
Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
title Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
title_full Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
title_fullStr Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
title_full_unstemmed Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
title_short Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses
title_sort identification of ribosomal protein family as immune-cell-related biomarkers of nafld by bioinformatics and experimental analyses
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235545/
https://www.ncbi.nlm.nih.gov/pubmed/37274336
http://dx.doi.org/10.3389/fendo.2023.1161269
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