Abstract Background and aims Dysregulation of alternative splicing has been implicated in various human diseases. However, the role of alternative splicing is poorly defined in asthma-chronic obstructive pulmonary disease overlap (ACO). In this study, we investigated the contribution of alternative splicing to ACO and emphasized the importance of understanding RNA isoform expression to elucidate its molecular mechanisms. Methods We employed two phenotypically distinct ACO mouse models for RNA sequencing and analyzed both gene expression and splicing patterns. Differential expression and splicing events were validated using RT-qPCR and rMATS analysis. Results Our analyses revealed that splicing-related genes were significantly regulated, suggesting that aberrant splicing regulation may represent a key pathogenic mechanism in ACO. More than 4,400 genes in the ACO-a model and 3,000 genes in the ACO-b model exhibited alternative splicing in lung tissues. Among these, the altered expression of Smarca4 and Pip4k2b was validated in ACO mouse lungs. Conclusions These findings uncover novel mechanisms underlying ACO pathogenesis. The study provides new insights into the regulatory networks connecting splicing isoforms with ACO development, highlighting potential biomarkers and therapeutic targets. This abstract is funded by: the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT), the Korean Environment Industry and Technology Institute through the Core Technology Development Project for Environmental Disease Prevention and Management, funded by the Korea Ministry of Environment
Hur et al. (Fri,) studied this question.
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