Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and ident...

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Published in:Aging (Albany, NY.) NY.), 2023-02, Vol.15 (5), p.1371-1393
Main Authors: Zheng, Peng-Fei, Zhou, Sen-Yu, Zhong, Chang-Qing, Zheng, Zhao-Fen, Liu, Zheng-Yu, Pan, Hong-Wei, Peng, Jian-Qiang
Format: Article
Language:English
Subjects:
Atrial Fibrillation - genetics
Gene Regulatory Networks
Healthy Volunteers
Humans
Methylation
Research Paper
RNA
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Summary:The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the and genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of and was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The and genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.204537