The miR-155-5p/SOCS1/NF-κB Axis Regulates Airway Smooth Muscle Dysfunction and is a Potential Therapeutic Candidate of Chronic Obstructive Pulmonary Disease.

Airway smooth muscle cell (ASMC) dysfunction, including altered cell viability, proliferation-apoptosis imbalance, and proinflammatory activation, contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD) associated inflammatory processes. We investigated the role of the miR-155-5p/SOCS1/NF-κB axis in these processes. We performed integrative analyses of GEO dataset mining (GSE5058), clinical samples from COPD patients, a mouse model of LPS/cigarette smoke–induced pulmonary inflammation, and mechanistic in vitro studies in ASMCs. The expression levels of miR-155-5p and SOCS1 were assessed by RT-qPCR and Western blotting. ASMC viability, apoptosis, invasion, cell cycling, and cytokine production were tested. Target interaction was validated by dual-luciferase reporter assay, and pathway involvement was assessed by analysis of the NF-κB signaling. miR-155-5p expression increased, and SOCS1 decreased in COPD lung tissues and serum (both p < 0.001), with an inverse correlation (r = − 0.48, p < 0.005). In mice, elevated miR-155-5p was associated with greater lung injury, higher TNF-α/IL-6 production, increased Cyclin D1 and phosphorylated NF-κB p65, and reduced p21, SOCS1, and cleaved caspase-3 (all p < 0.05). In ASMCs, miR-155-5p promoted cell viability, invasion, S-phase entry, apoptosis resistance, and cytokine production (all p < 0.05). miR-155-5p directly bound the SOCS1 3′UTR. miR-155-5p inhibition or SOCS1 overexpression attenuated NF-κB activation and rescued these phenotypes; SOCS1 overexpression reduced ~ 70% of miR-155-5p mimic–induced changes. The miR-155-5p/SOCS1/NF-κB axis contributes to ASMC dysfunction in COPD, supporting miR-155-5p as a potential therapeutic candidate.