Supplementary file 1_Exercise-responsive circTSN as a potential systemic biomarker during COPD rehabilitation.docx

ObjectiveChronic 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.
MethodsWe 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.
ResultscircTSN 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. Mechanistically, circTSN was found to be cytoplasmically enriched and functioned as a molecular sponge for miR-144-3p. This axis subsequently modulated the expression of key inflammatory genes in BEAS-2B airway epithelial cells, 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.
ConclusioncircTSN may serve as a molecular sensor linking changes in the pulmonary environment to the body’s broader adaptive responses during exercise therapy. This discovery offers crucial mechanistic insight into how exercise benefits individuals with COPD, highlighting circTSN as a valuable target for future molecular monitoring and therapeutic strategies.