Hsa-Mir-320c, Hsa-Mir-200c-3p, and Hsa-Mir-449c-5p as Potential Specific miRNA Biomarkers of COPD: A Pilot Study

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease commonly induced by cigarette smoke. The expression of miRNAs can be altered in patients with COPD and could be used as a biomarker. We aimed to identify a panel of miRNAs in bronchoalveolar lavage (BAL) to differentiate COPD patients from smokers and non-smokers with normal lung function. Accordingly, forty-five subjects classified as COPD, smokers, and non-smokers (n = 15 per group) underwent clinical, functional characterization and bronchoscopy with BAL. The mean age of the studied population was 61.61 ± 12.95 years, BMI 25.72 ± 3.82 Kg/m2, FEV1/FVC 68.37 ± 12.00%, and FEV1 80.07 ± 23.63% predicted. According to microarray analysis, three miRNAs of the most upregulated were chosen: miR-320c, miR-200c-3p, and miR-449c-5p. These miRNAs were validated by qPCR and were shown to be differently expressed in COPD patients. ROC analysis showed that these three miRNAs together had an area under the curve of 0.89 in differentiating COPD from controls. Moreover, in silico analysis of candidate miRNAs by DIANA-miRPath showed potential involvement in the EGFR and Hippo pathways. These results suggest a specific 3-miRNA signature that could be potentially used as a biomarker to distinguish COPD patients from smokers and non-smoker subjects.

Altered Extracellular Vesicle-Derived Protein and microRNA Signatures in Bronchoalveolar Lavage Fluid from Patients with Chronic Obstructive Pulmonary Disease

“…These contrasting effects in different compartments and diseases suggest that miRNA expression might depend on specific cell type activation within a particular context. Regarding the up-regulation of miR-449c-5p, our results align with a study in COPD demonstrating a higher expression of this miRNA in BAL-derived extracellular miRNAs of COPD patients compared to smokers and nonsmokers [37]. Similarly, miR-10a-5p was found to be higher in bronchial epithelial cells from patients with asthma and COPD compared to controls [38].…”

miRNA‐449c‐5p regulates the JAK‐STAT pathway in inhibiting cell proliferation and invasion in human breast cancer cells by targeting ERBB2

“…MiR‐449c‐5p was remarkably increased in palatal cells 21 . It was a potential therapeutical target for chronic obstructive pulmonary disease (COPD), which was proved by a pilot study 22 . In nasopharyngeal carcinoma (NPC), miR‐449c‐5p was differently expressed 23 .…”

“… 21 It was a potential therapeutical target for chronic obstructive pulmonary disease (COPD), which was proved by a pilot study. 22 In nasopharyngeal carcinoma (NPC), miR‐449c‐5p was differently expressed. 23 The research articles indicated that miR‐449c‐5p regulated the STAT6 signalling pathway of acute cerebral infarction (ACI).…”