Exercise-Responsive circTSN as a Potential Systemic Biomarker During COPD Rehabilitation

Lei Zhao¹xiaoxiang liu^2*fan bai²huali zhang¹haizhu zeng¹Rreshma akter³

• ¹Shanghai Pudong New Area Gongli Hospital, Shanghai, China
• ²The First People's Hospital of Changde City, Changde, China
• ³Morgan State University, Baltimore, United States

Objective: Chronic Obstructive Pulmonary Disease (COPD) features both pulmonary and systemic manifestations. While exercise is a proven therapeutic strategy, the specific non-coding RNAs mediating the systemic adaptive response remain largely unknown. This study aims to identify circTSN as a key circular RNA (circRNA) involved in exercise-induced adaptation in COPD. Methods: We performed a prospective cohort study using peripheral blood RNA sequencing in COPD patients (n = 4) before and after a 12-week exercise intervention, and validated the expression changes with RT-qPCR (n = 18). The mechanism of circTSN (hsa-circ_0003789) was investigated using a COPD mouse model, dual-luciferase reporter assays in 293T cells, and functional in vitro experiments in BEAS-2B airway epithelial cells. Results: circTSN expression was significantly upregulated post-exercise in both COPD patients and the mouse model, and this change was decoupled from its host gene, establishing it as an independent molecular marker. circTSN was found to be cytoplasmically enriched and functioned as a molecular sponge for miR-144-3p. This axis subsequently modulated the expression of inflammatory genes in BEAS-2B, including GATA6, IL-6, IL-1β, and TNF-α, linking the airway epithelium to systemic inflammation. Furthermore, in vivo, circTSN and miR-144-3p were inversely correlated, establishing this ceRNA axis as critical for exercise-mediated lung adaptation. Conclusion: circTSN may serve as a molecular sensor linking changes in the pulmonary environment to the body's broader adaptive responses during exercise. This discovery offers crucial mechanistic insight into how exercise benefits individuals with COPD.