Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases

• Published in: BMC pulmonary medicine Vol. 23; no. 1; p. 210
• Main Authors: Wang, Yuting, Wang, Jiaxi, Yan, Zhanfeng, Liu, Siming, Xu, Wenlong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16-06-2023; BioMed Central; BMC
• Subjects: Algorithms; Allergic diseases; Allergic rhinitis; Allergies; Analysis; Asthma; Care and treatment; Diagnosis; Epigenetics; Gene expression; Gene set enrichment analysis; Genetic aspects; Glucocorticoids; Hay-fever; Helper cells; Hypersensitivity; Immune microenvironment; Infiltration; Lymphocytes T; m6A modification; m6A regulators; Machine learning; Macrophages; Methylprednisolone; Methyltransferases; METTL14; Microenvironments; N6-methyladenosine; Physiology; Post-transcription; Prediction models; Proteins; Pulmonology; Respiratory allergic diseases; RNA modification; Sensitivity analysis; Software; China; Immune microenvironment; METTL14; m6A modification; Allergic rhinitis; m6A regulators; Respiratory allergic diseases; Asthma
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/s12890-023-02499-0

RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics.
We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication.
In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids.
Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.