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m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of periodontitis |
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| Authors: | Xiaoqi Zhang Shizhen Zhang Xinyu Yan Yue Shan Lu Liu Jing Zhou Qianyun Kuang Minqi Li Hu Long Wenli Lai |
| Affiliation: | 1. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Formal analysis (lead), Methodology (lead), Writing - original draft (lead);2. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Data curation (lead);3. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Software (lead), Visualization (lead);4. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Methodology (lead);5. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Validation (equal);6. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Visualization (supporting);7. Department of Bone Metabolism, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Chengdu, China Contribution: Supervision (equal), Writing - review & editing (equal);8. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China Contribution: Project administration (equal);9. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China |
| Abstract: | 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. |
| Keywords: | epigenetics immune microenvironment immunity m6A periodontitis RNA modification |