4.5 Article

m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of periodontitis

期刊

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 7, 页码 3634-3645

出版社

WILEY
DOI: 10.1111/jcmm.16469

关键词

epigenetics; immune microenvironment; immunity; m6A; periodontitis; RNA modification

资金

  1. Fundamental Research Program - Department of Science and Technology of Sichuan Province [2018JY0558]

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Through the study of 310 periodontitis samples, it was found that m6A modification plays a crucial role in the immune microenvironment of periodontitis, involving regulation of immune cell infiltration, immune reaction gene sets, HLA genes, and more. Some m6A regulators were found to be dysregulated, and a signature of 15 m6A regulators can effectively distinguish periodontitis from control samples.
The role of epigenetic regulation in immunity is emerging, especially for RNA N6-methyladenosine (m6A) modification. However, little is known about the role of m6A in the regulation of the immune microenvironment of periodontitis. Thus, we aim to investigate the impact of m6A modification in periodontitis immune microenvironment. The RNA modification patterns mediated by 23 m6A-regulators were systematically evaluated in 310 periodontitis samples. The impact of m6A modification on immune microenvironment characteristics was explored, including infiltrating immunocytes, immune reaction gene-sets and HLAs (human leukocyte antigen) gene. m6A phenotype-related immune genes were also identified. 17 m6A regulators were dysregulated and a 15-m6A regulator signature can well distinguish periodontitis and control samples. ALKBH5 and FMR1 are closely related to infiltrating monocyte abundance. ELAVL1 and CBLL1 are significant regulators in immune reaction of TNF_Family_Members_Receptors and Cytokine. The expression of HLA-B and HLA-DOA is affected by ALKBH5 and LRPPRC. 3 distinct RNA modification patterns mediated by 23 m6A regulators were identified. They differ from immunocyte abundance, immune reaction and HLA gene. 1631 m6A phenotype-related genes and 70 m6A-mediated immune genes were identified, and the biological functions of these were explored. Our finding demonstrated the m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment of periodontitis.

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