Details

Autor(en) / Beteiligte

• Zeng, Zhimin
• Liang, Yuxia
• Xu, Changyi
• Tan, Weiping
• Du, Lijuan
• Liu, Yangli
• Chen, Fengjia
• Guo, Yubiao

Titel

Novel DNA Promoter Hypermethylation in Nasal Epithelium of Asthma

Ist Teil von

• Combinatorial chemistry & high throughput screening, 2023-01, Vol.26 (10), p.1879-1887

Erscheinungsjahr

2023

Beschreibungen/Notizen

• Background: Abnormal epigenetic alterations influenced by external factors and affecting DNA expression contribute to the development of asthma. However, the role of nasal epithelium in airway inflammation remains unknown. Objective: The objective of this study is to identify novel DNA promoter hypermethylation, which completely suppresses mRNA expression in nasal epithelial of asthma. Methods: Microarray datasets were downloaded from the Gene Expression Omnibus [GEO] database. Gene expression and DNA promoter methylation sites in key correlated modules between asthma and normal were identified by weighted gene co-expression network analysis [WGCNA]. Gene Ontology and KEGG were conducted to analyse the function of genes. Further validation was performed in human BEAS-2B cells challenged by IL-4 or IL-13. Results: Lightcyan, lightgreen, midnightblue, cyan and tan modules in mRNA expression dataset showed a close relationship with asthma, in which genes were enriched in TNF, IL-17, ErbB, MAPK and Estrogen signalling pathways. Blue and turquoise modules in methylation profiling dataset were associated with asthma. 49 lowly expressed genes were identified to be correlated with aberrant DNA hypermethylation of promoters. Among these genes, the mRNA levels of BCL10, GADD45B, LSR and SQSTM1 were downregulated in BEAS-2B cells challenged with IL-4 or IL-13. Conclusion: Four potential genes in nasal epithelium, by hypermethylating their own DNA promoter, might mediate the inflammatory response in the pathogenesis of asthma. Analyzing epigenomic data by integrated bioinformatics helps to understand the role of DNA methylation in asthma, with the goal of providing new perspectives for diagnosis and therapy.