| Popis: |
Asthma is a complicated chronic airway inflammatory disease caused by the interaction of genetic susceptibility and environmental impact. Although biologists have explored the pathogenesis of asthma in various aspects, the exact molecular mechanism continues to be elusive. In this study, we conducted a modular study of asthma-related genes to explore their core pathogenic driving genes. Firstly, the expression profiles of normal, mild to moderate and severe asthma patients were analyzed to screen the differentially expressed genes. Secondly, differential genes of asthma were integrated, co-expressed and clustered into modules. Next, enrichment of GO function and KEGG pathway of module genes were analyzed. Finally, non-coding RNA (ncRNA) and transcription factors that regulate modules are predicted by hypergeometric test. In summary, we have obtained 14 co-expression modules, among which CDCA5, JUNB and other genes are significantly differentially expressed in asthmatic patients, and have an active regulatory role in dysfunction module, so they are recognized as asthma-driving genes. Enrichment results showed that module genes were significantly involved in cell growth, transcription factor activity, cellular response to drugs and the transport of various ions. In addition, they also radically regulate Wnt, TGF-beta, JAK-STAT and extracellular matrix signaling pathways. Finally, we identified significant regulatory dysfunction modules of ncRNA pivot (including miR-181a-5p and let-7d-5p) and TF pivot (including NFKB1, ESR1 and MYC). Overall, our work has uncovered a co-expression network involved in the regulation of core pathogenic genes of asthma. It helps to reveal the core dysfunction modules and potential regulatory factors of this disease, and to enhance our understanding of the molecular mechanisms of asthma-related diseases. |
