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Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease

BACKGROUND: Several human diseases are associated with aberrant expression of regulators involved in N6-methyladenosine (m6A) RNA modification. However, their role in aortic valve calcification (AVC) is largely unknown. The aim of this study was to determine the general expression pattern and potent...

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Autores principales: Chen, Jun-Yu, Xiong, Tao, Sun, Ya-Ru, Cong, Juan, Gong, Jing-Shuai, Peng, Lei, Rong, Yu-Wang, Wang, Zi-Yao, Chang, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511183/
https://www.ncbi.nlm.nih.gov/pubmed/36172101
http://dx.doi.org/10.21037/atm-22-3627
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author Chen, Jun-Yu
Xiong, Tao
Sun, Ya-Ru
Cong, Juan
Gong, Jing-Shuai
Peng, Lei
Rong, Yu-Wang
Wang, Zi-Yao
Chang, Qing
author_facet Chen, Jun-Yu
Xiong, Tao
Sun, Ya-Ru
Cong, Juan
Gong, Jing-Shuai
Peng, Lei
Rong, Yu-Wang
Wang, Zi-Yao
Chang, Qing
author_sort Chen, Jun-Yu
collection PubMed
description BACKGROUND: Several human diseases are associated with aberrant expression of regulators involved in N6-methyladenosine (m6A) RNA modification. However, their role in aortic valve calcification (AVC) is largely unknown. The aim of this study was to determine the general expression pattern and potential function of m6A regulators in AVC by bioinformatics methods. METHODS: We obtained AVC datasets from the Gene Expression Omnibus (GEO). The identification of m6A-related differentially expressed genes (DEGs) and the Consensus Clustering method was performed to type AVC individuals based DEGs. Then, we quantified the effect of typing by principal component analysis (PCA). Next, we performed the weighted gene co-expression network analysis (WGCNA) and identified the main modules as well as functional analysis. Additionally, the key genes were screened by protein-protein interaction network (PPIN) analysis and identifying important genes of important modules. We again typed AVC individuals by the same method using key genes. Finally, we evaluated the link between key genes and immune infiltration. RESULTS: We discovered that METTL14, ZC3H13, FTO, FMR1, HNRNPA2B1, HNRNPC, LRPPRC, YTHDC1, YTHDC2, and YTHDF1 expression levels decreased considerably in AVC tissues. Based on 10 genes, we typed 240 AVC samples as clusters A and B. We assessed the immune cell content in 240 samples using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and found that B cell memory, CD8 T cells, T follicular helper cells, monocytes, M0 macrophages, resting dendritic cells (DCs), and interleukin-10 (IL-10) were concentrated in the cluster A group. Additionally, based on the important WGCNA modules, we identified 7 key genes. Next, 240 samples were retyped based on 7 key genes; we found that T cells CD8, T cells CD4 memory activated, T cells follicular helper, and macrophages M1 were significantly increased in gene cluster-1. Finally, we performed functional enrichment of gene cluster-typed samples, showing potential functional differences between different types. CONCLUSIONS: Our study provides a review of the m6A regulators’ expression pattern and functional importance in human AVC. The data from this study might serve as a significant resource for future mechanistic and therapeutic investigations into the role of critical m6A regulators in AVC.
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spelling pubmed-95111832022-09-27 Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease Chen, Jun-Yu Xiong, Tao Sun, Ya-Ru Cong, Juan Gong, Jing-Shuai Peng, Lei Rong, Yu-Wang Wang, Zi-Yao Chang, Qing Ann Transl Med Original Article BACKGROUND: Several human diseases are associated with aberrant expression of regulators involved in N6-methyladenosine (m6A) RNA modification. However, their role in aortic valve calcification (AVC) is largely unknown. The aim of this study was to determine the general expression pattern and potential function of m6A regulators in AVC by bioinformatics methods. METHODS: We obtained AVC datasets from the Gene Expression Omnibus (GEO). The identification of m6A-related differentially expressed genes (DEGs) and the Consensus Clustering method was performed to type AVC individuals based DEGs. Then, we quantified the effect of typing by principal component analysis (PCA). Next, we performed the weighted gene co-expression network analysis (WGCNA) and identified the main modules as well as functional analysis. Additionally, the key genes were screened by protein-protein interaction network (PPIN) analysis and identifying important genes of important modules. We again typed AVC individuals by the same method using key genes. Finally, we evaluated the link between key genes and immune infiltration. RESULTS: We discovered that METTL14, ZC3H13, FTO, FMR1, HNRNPA2B1, HNRNPC, LRPPRC, YTHDC1, YTHDC2, and YTHDF1 expression levels decreased considerably in AVC tissues. Based on 10 genes, we typed 240 AVC samples as clusters A and B. We assessed the immune cell content in 240 samples using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and found that B cell memory, CD8 T cells, T follicular helper cells, monocytes, M0 macrophages, resting dendritic cells (DCs), and interleukin-10 (IL-10) were concentrated in the cluster A group. Additionally, based on the important WGCNA modules, we identified 7 key genes. Next, 240 samples were retyped based on 7 key genes; we found that T cells CD8, T cells CD4 memory activated, T cells follicular helper, and macrophages M1 were significantly increased in gene cluster-1. Finally, we performed functional enrichment of gene cluster-typed samples, showing potential functional differences between different types. CONCLUSIONS: Our study provides a review of the m6A regulators’ expression pattern and functional importance in human AVC. The data from this study might serve as a significant resource for future mechanistic and therapeutic investigations into the role of critical m6A regulators in AVC. AME Publishing Company 2022-09 /pmc/articles/PMC9511183/ /pubmed/36172101 http://dx.doi.org/10.21037/atm-22-3627 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Chen, Jun-Yu
Xiong, Tao
Sun, Ya-Ru
Cong, Juan
Gong, Jing-Shuai
Peng, Lei
Rong, Yu-Wang
Wang, Zi-Yao
Chang, Qing
Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease
title Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease
title_full Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease
title_fullStr Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease
title_full_unstemmed Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease
title_short Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease
title_sort modification of m6a mediates tissue immune microenvironment in calcific aortic valve disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511183/
https://www.ncbi.nlm.nih.gov/pubmed/36172101
http://dx.doi.org/10.21037/atm-22-3627
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