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

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.

Elevated N6-Methyladenosine RNA Levels in Peripheral Blood Immune Cells: A Novel Predictive Biomarker and Therapeutic Target for Colorectal Cancer

“…Additionally, monocytes were identified as the immune cells most strongly associated with the increased regulation of upregulated m 6 A levels in peripheral blood of CRC patients (Figure 4). It has been noted that the presence of a large number of m 6 A-modified infiltrating immune cells in the tumor tissue microenvironment promotes tumor progression (33,34). Furthermore, imbalanced m 6 A regulation strongly conferred immune disruption and tumor evasion, primarily by affecting immune cell migration, rather than apoptosis or survival (35).…”

Crosstalk between RNA-Binding Proteins and Immune Microenvironment Revealed Two RBP Regulatory Patterns with Distinct Immunophenotypes in Periodontitis

“…The evaluation of the overall status of immune infiltration in periodontitis and healthy samples was conducted using the same method as we have illustrated in the previous study, and the results were consistent [17,18].…”

“…The evaluation of the overall status of immune infiltration in periodontitis and healthy samples was conducted using the same method as we have illustrated in the previous study, and the results were consistent [ 17 , 18 ]. In brief, single-sample Gene Set Enrichment Analysis (ssGSEA) was conducted to evaluate the relative enrichment score of immunocytes and the activity of immune-related pathways.…”

Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma

“…The relative enrichment of infiltrating immunocytes and the activity of immune pathways were determined by single-sample gene-set enrichment analysis (ssGSEA). 21 , 22 The gene sets used to determine the composition of immunocytes were obtained from the previous study, 23 which included 28 widely used tumor infiltrated immunocytes such as T cell family and B cell family, and we only presented the statistically significant immunocytes in the results figures. The gene sets used to evaluate the activity of immune-related pathways were obtained from the database ImmPort ( http://www.immport.org), 24 which contains 17 immunologically relevant lists of genes curated with functions and Gene Ontology terms.…”