Exercise-responsive circTSN as a potential systemic biomarker during COPD rehabilitation.

Area of Science:

• Molecular Biology
• Pulmonology
• Genetics

Background:

• Chronic Obstructive Pulmonary Disease (COPD) involves systemic and pulmonary issues.
• Exercise improves COPD, but the underlying molecular mechanisms are unclear.
• Non-coding RNAs' role in exercise adaptation in COPD is largely unknown.

Purpose of the Study:

• Identify circular RNAs (circRNAs) mediating exercise adaptation in COPD.
• Investigate circTSN (hsa-circ_0003789) as a key circRNA in this process.

Main Methods:

• Prospective cohort study with peripheral blood RNA sequencing in COPD patients.
• RT-qPCR validation, COPD mouse model, dual-luciferase reporter assays, and in vitro cell experiments.
• Investigated circTSN's mechanism as a competing endogenous RNA (ceRNA) for miR-144-3p.

Main Results:

• circTSN expression increased post-exercise in COPD patients and a mouse model, independent of its host gene.
• circTSN acts as a molecular sponge for miR-144-3p in airway epithelial cells.
• The circTSN-miR-144-3p axis modulated inflammatory genes and was critical for exercise-mediated lung adaptation.

Conclusions:

• circTSN functions as a molecular sensor linking pulmonary changes to systemic adaptation during exercise in COPD.
• This finding provides mechanistic insight into exercise benefits for COPD.
• circTSN represents a potential target for monitoring and therapeutic strategies in COPD.