Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is primarily caused by cigarette smoke (CS)‐induced chronic inflammation. In this study, we investigated the function and mechanism of action of the long non‐coding RNA (lncRNA) taurine‐up‐regulated gene 1 (TUG1) in CS‐induced COPD. We found that the expression of TUG1 was significantly higher in the sputum cells and lung tissues of patients with COPD as compared to that in non‐smokers, and negatively correlated with the percentage of predicted forced expiratory volume in 1 second. In addition, up‐regulation of TUG1 was observed in CS‐exposed mice, and knockdown of TUG1 attenuated inflammation and airway remodelling in a mouse model. Moreover, TUG1 expression was higher in CS extract (CSE)‐treated human bronchial epithelial cells and lung fibroblasts, whereas inhibition of TUG1 reversed CSE‐induced inflammation and collagen deposition in vitro. Mechanistically, TUG1 promoted the expression of dual‐specificity phosphatase 6 (DUSP6) by sponging miR‐145‐5p. DUSP6 overexpression reversed TUG1 knockdown‐mediated inhibition of inflammation and airway remodelling. These findings suggested an important role of TUG1 in the pathological alterations associated with CS‐mediated airway remodelling in COPD. Thus, TUG1 may be a promising therapeutic target in CS‐induced airway inflammation and fibroblast activation.

Identifying Prognostic Lncrnas Based on A ceRNA Regulatory Network in Laryngeal Squamous Cell Carcinoma

“…For example, lnc HOTAIR can act as a molecular sponge for both miR-206 and miR-124 [15,34]. Both lncRNA TUG1 and lncRNA PVT1 can interact with miR-145 [35,36]. Similarly, the interaction between miRNA and mRNA is not the only correspondence relationship.…”

The Potential Roles of Exosomes in Chronic Obstructive Pulmonary Disease

“…Gu's research shows that taurine-upregulated gene 1 (TUG1) expression is enhanced in COPD patients, and TUG1 inhibits the expression of miR-145-5pp/DUSP6 axis to promote airway remodelings such as TGF-β1, mucus hypersecretion, collagen 1 and α-SMA and inflammation such as increased IL-6 and pulmonary neutrophil infiltration ( 67 ). TUG1, combined with CDKN2B-AS1, can be used to predict acute exacerbation in COPD patients ( 68 ).…”

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review)

“…In this context, taurine upregulated gene 1 (TUG1) is a lncRNA, that has been identified due to its upregulation during retinal development in response to taurine treatment ( 296 ). Accumulating evidence has supported the overexpression of lncRNA TUG1 in different disease contexts, including MS ( 297 ), diabetes mellitus (DM) ( 298 ), chronic kidney disease (CKD) ( 299 ), and chronic obstructive pulmonary disease (COPD) ( 300 ). In the diabetic nephropathy and CKD, one potential mechanism underlying the action of lncRNA TUG1 is based on increasing the transcription of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1), thus enabling the improved mitochondrial bioenergetics ( 299 , 301 ).…”