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Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia
Tianping Bao1, Haiyan Zhu1, Mengmeng Ma1
1Department of Neonatology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, No. 1 Western Huanghe Road, Huai'an, 223300, Jiangsu, China.
Abstract:
N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of bronchopulmonary dysplasia (BPD) remains poorly characterized. Thus, the purpose of this investigation was to evaluate the effects of m6A RNA methylation regulators on the development of BPD. BPD-related transcriptome data were downloaded from the GEO database. Differentially expressed m6A methylation regulators between BPD and control group were identified. Consensus clustering was conducted for the classification of BPD and association between clusters and BPD phenotypes were explored. Analysis of differentially expressed genes (DEGs) and immune-related DEGs was performed. The GSEA, GO and KEGG analyses were used to interpret the functional enrichments. The composition of immune cell subtypes in BPD subsets was predicted by CIBERSORT analysis. Compared with the control group, expression of most m6A regulators showed significant alteration, especially for IGF2BP1/2/3. BPD was classified into 2 subsets, and cluster 1 was correlated with severe BPD. Furthermore, the results of functional enrichment analyses showed a disturbed immune-related signaling pathway. Based on CIBERSORT analysis, we found that the proportion of immune cell subsets changed between cluster 1 and cluster 2. Our study revealed the implication of m6A methylation regulators in the development of BPD, which might provide a novel insight for the diagnosis and treatment of BPD.
Insights
N6-methyladenosine (m6A) RNA methylation regulators are altered in bronchopulmonary dysplasia (BPD). These changes impact immune pathways and may offer new diagnostic and therapeutic targets for BPD.
Area of Science:
- Epigenetics and Respiratory Medicine
Background:
- N6-methyladenosine (m6A) is a crucial RNA modification regulating gene expression.
- The role of m6A in bronchopulmonary dysplasia (BPD) development is not well understood.
Purpose of the Study:
- To investigate the impact of m6A RNA methylation regulators on BPD development.
- To identify potential diagnostic and therapeutic strategies for BPD based on m6A regulators.
Main Methods:
- Downloaded and analyzed BPD-related transcriptome data from the GEO database.
- Identified differentially expressed m6A regulators and performed consensus clustering for BPD classification.
- Utilized Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment.
- Predicted immune cell subtype composition using CIBERSORT analysis.
Main Results:
- Most m6A regulators showed significant expression alterations in BPD, particularly IGF2BP1/2/3.
- BPD was classified into two subsets, with cluster 1 associated with more severe disease.
- Functional enrichment analyses revealed dysregulated immune-related signaling pathways.
- Immune cell subset proportions differed significantly between the two BPD clusters.
Conclusions:
- m6A methylation regulators play a significant role in BPD pathogenesis.
- Altered m6A regulator expression and immune cell infiltration are characteristic of BPD.
- These findings suggest m6A regulators as potential biomarkers and therapeutic targets for BPD.
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