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Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis

BACKGROUND: N6-methyladenosine (m6A) is a universal RNA modification pattern regulated by multiple m6A regulators. In osteoarthritis (OA), m6A regulators influence disease progression by regulating cartilage degradation. However, the function of m6A regulators in synovial tissue remains unclear. In...

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Autores principales: Bian, Ashuai, Wang, Changming, Zhang, Haotian, Yan, Yiqun, Zhang, Linlin, Cheng, Wendan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373247/
https://www.ncbi.nlm.nih.gov/pubmed/37496062
http://dx.doi.org/10.1186/s13018-023-03933-z
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author Bian, Ashuai
Wang, Changming
Zhang, Haotian
Yan, Yiqun
Zhang, Linlin
Cheng, Wendan
author_facet Bian, Ashuai
Wang, Changming
Zhang, Haotian
Yan, Yiqun
Zhang, Linlin
Cheng, Wendan
author_sort Bian, Ashuai
collection PubMed
description BACKGROUND: N6-methyladenosine (m6A) is a universal RNA modification pattern regulated by multiple m6A regulators. In osteoarthritis (OA), m6A regulators influence disease progression by regulating cartilage degradation. However, the function of m6A regulators in synovial tissue remains unclear. In this work, we investigated the biological significance of m6A regulators in osteoarthritic synovitis. METHODS: Datasets were acquired from Gene Expression Omnibus. Differential analysis of merged data identified the differentially expressed m6A regulators. Machine learning models were used to evaluate genetic importance. To predict disease risk, a nomogram was constructed based on above m6A regulators. Cluster analysis divided the OA sample into different subgroups. Immune infiltration revealed the immune m6A regulators, which were validated using clinical samples. Eventually, a competing endogenous RNA (ceRNA) network was constructed. RESULTS: We acquired five differentially expressed m6A regulators and a random forest model. The nomogram accurately predicted disease risk. We identified 122 differentially expressed genes between two m6A subgroups. The analysis of immune infiltration showed that YTHDF2 was an immune-related m6A regulator closely related with macrophages. In clinical samples, the protein and mRNA contents of YTHDF2 were consistent with the results of bioinformatic analysis. The ceRNA network based on YTHDF2 revealed 75 lncRNA nodes and 19 miRNA nodes. CONCLUSION: YTHDF2 has a high diagnostic value in the synovitis of OA and significantly influences the immune status of patients. Hence, YTHDF2, a critical m6A regulator, may provide a biomarker for diagnosis and immune therapy of osteoarthritic synovitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-03933-z.
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spelling pubmed-103732472023-07-28 Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis Bian, Ashuai Wang, Changming Zhang, Haotian Yan, Yiqun Zhang, Linlin Cheng, Wendan J Orthop Surg Res Research Article BACKGROUND: N6-methyladenosine (m6A) is a universal RNA modification pattern regulated by multiple m6A regulators. In osteoarthritis (OA), m6A regulators influence disease progression by regulating cartilage degradation. However, the function of m6A regulators in synovial tissue remains unclear. In this work, we investigated the biological significance of m6A regulators in osteoarthritic synovitis. METHODS: Datasets were acquired from Gene Expression Omnibus. Differential analysis of merged data identified the differentially expressed m6A regulators. Machine learning models were used to evaluate genetic importance. To predict disease risk, a nomogram was constructed based on above m6A regulators. Cluster analysis divided the OA sample into different subgroups. Immune infiltration revealed the immune m6A regulators, which were validated using clinical samples. Eventually, a competing endogenous RNA (ceRNA) network was constructed. RESULTS: We acquired five differentially expressed m6A regulators and a random forest model. The nomogram accurately predicted disease risk. We identified 122 differentially expressed genes between two m6A subgroups. The analysis of immune infiltration showed that YTHDF2 was an immune-related m6A regulator closely related with macrophages. In clinical samples, the protein and mRNA contents of YTHDF2 were consistent with the results of bioinformatic analysis. The ceRNA network based on YTHDF2 revealed 75 lncRNA nodes and 19 miRNA nodes. CONCLUSION: YTHDF2 has a high diagnostic value in the synovitis of OA and significantly influences the immune status of patients. Hence, YTHDF2, a critical m6A regulator, may provide a biomarker for diagnosis and immune therapy of osteoarthritic synovitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-03933-z. BioMed Central 2023-07-27 /pmc/articles/PMC10373247/ /pubmed/37496062 http://dx.doi.org/10.1186/s13018-023-03933-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Bian, Ashuai
Wang, Changming
Zhang, Haotian
Yan, Yiqun
Zhang, Linlin
Cheng, Wendan
Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis
title Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis
title_full Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis
title_fullStr Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis
title_full_unstemmed Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis
title_short Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis
title_sort diagnostic value and immune infiltration characterization of ythdf2 as a critical m6a regulator in osteoarthritic synovitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373247/
https://www.ncbi.nlm.nih.gov/pubmed/37496062
http://dx.doi.org/10.1186/s13018-023-03933-z
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