MicroRNA-199a-5p Is Associated With Hypoxia-Inducible Factor-1α Expression in Lungs From Patients With COPD

Background: MicroRNAs (miRNAs) are small noncoding RNAs that silence target gene expression posttranscriptionally, and their impact on gene expression has been reported in various diseases. It has been reported that the expression of the hypoxia-inducible factor-1 alpha (HIF-1 alpha) is reduced and that of p53 is increased in lungs from patients with COPD. However, the role of miRNAs associated with these genes in lungs from patients with COPD is unknown. Methods: Lung tissue samples from 55 patients were included in this study. Total RNA, miRNA, and protein were extracted from lung tissues and used for reverse transcriptase polymerase chain reaction and Western blot analysis. Cell culture experiments were performed using cultured human pulmonary microvascular endothelial cells (HPMVECs). Results: miR-34a and miR-199a-5p expressions were increased, and the phosphorylation of AKT was decreased in the lung tissue samples of patients with COPD. The miA-199a-5p expression was correlated with HIF-1 alpha protein expression in the lungs of patients with COPD. Transfection of HPMVECs with the miR-199a-5p precursor gene decreased HIF-1 alpha protein expression, and transfection with the miR-34a precursor gene increased miR-199a-5p expression. Conclusions: These data suggest that miR-34a and miR-199a-5p contribute to the pathogenesis of COPD, and these miRNAs may also affect the HIF-1 alpha-dependent lung structure maintenance program. CHEST 2012; 142 (3):663-672