RNA alternative splicing events as biomarkers for asthma-chronic obstructive pulmonary disease overlap

<bold>Background and aims:</bold> Dysregulation of alternative splicing is implicated in many human diseases. However, the role of alternative splicing is poorly defined in asthma-chronic obstructive pulmonary disease overlap (ACO). Here, we aimed to examine the role of alternative splicing in ACO. <bold>Methods:</bold> Two phenotypes of ACO mouse model were utilized for RNA sequencing, and the expression and splicing data were analyzed. The changes in expression and splicing event types were verified using RT-qPCR and rMATS analysis. <bold>Results:</bold> Our results showed that splicing-related genes were regulated, suggesting that splicing regulation may be a key mechanism in ACO. We also found that more than 4,400 (in ACO-a) and 3,000 (in ACO-b) genes displayed alternative splicing in the lungs of mice with ACO. We validated the expression of Smarca4 and Pip4k2b in the lungs of mice with ACO. <bold>Conclusions:</bold> These findings revealed novel mechanisms related to ACO pathogenesis. Our study provides insights into the regulatory mechanisms linking splicing isoforms to ACO and serving as biomarkers and therapeutic targets.