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

Xiaoqi Zhang1, Shizhen Zhang1, Xinyu Yan1

  • 1Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China.

Insights

Epigenetic RNA N6-methyladenosine (m6A) modification significantly impacts the periodontitis immune microenvironment. This study reveals m6A regulators are key to immune cell infiltration and function in periodontitis.

Area of Science:

  • Immunology
  • Epigenetics
  • Oral Biology

Background:

  • Epigenetic regulation, particularly RNA N6-methyladenosine (m6A) modification, is increasingly recognized for its role in immunity.
  • The specific involvement of m6A in the immune microenvironment of periodontitis remains largely unexplored.

Purpose of the Study:

  • To investigate the impact of m6A modification on the immune microenvironment in periodontitis.
  • To identify m6A regulators and their associated immune characteristics in periodontitis.

Main Methods:

  • Systematic evaluation of RNA modification patterns mediated by 23 m6A regulators in 310 periodontitis samples.
  • Analysis of m6A modification's impact on infiltrating immunocytes, immune reaction gene-sets, and human leukocyte antigen (HLA) genes.
  • Identification of m6A phenotype-related immune genes.

Main Results:

  • 17 m6A regulators were found to be dysregulated, with a 15-m6A regulator signature distinguishing periodontitis from control samples.
  • Specific regulators (ALKBH5, FMR1, ELAVL1, CBLL1, LRPPRC) were linked to monocyte abundance, immune reactions (TNF family, Cytokine), and HLA gene expression.
  • Three distinct m6A modification patterns were identified, correlating with variations in immunocyte infiltration, immune response, and HLA gene expression.
  • 1631 m6A phenotype-related genes and 70 m6A-mediated immune genes were identified and functionally explored.

Conclusions:

  • m6A modification plays a critical role in shaping the diverse and complex immune microenvironment of periodontitis.
  • m6A regulators represent potential targets for understanding and potentially treating periodontitis-associated immune dysregulation.

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