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Background  MicroRNAs (MiRNA) are small non-coding RNAs that regulate gene expression. The aim of this study was to identify miRNAs differentially expressed between mild and moderately emphysematous lung, as well as their functional target mRNAs. Resected lung from patients with COPD undergoing lung cancer surgery was profiled using miRNA (Agilent Human miRNA profiler G4470 V1.01) and mRNA (OperonV2.0) microarrays. Cells of lung origin (BEAS-2B and HFL1) were profiled using mRNA microarrays (Illumina HumanHT-12 V3) after  in vitro  manipulation.    Results  COPD patients had mean (SD) age 68 (6) years, FEV 1  72 (17)% predicted and gas transfer (KCO) 70 (10)% predicted. Five miRNAs ( miR-34c ,  miR-34b ,  miR-149 ,  miR-133a  and  miR-133b ) were significantly down-regulated in lung from patients with moderate compared to mild emphysema as defined by gas transfer ( p  < 0.01).  In vitro  upregulation of  miR-34c  in respiratory cells led to down-regulation of predicted target mRNAs, including  SERPINE1 ,  MAP4K4 ,  ZNF3 ,  ALDOA  and  HNF4A . The fold change in ex-vivo expression of all five predicted target genes inversely correlated with that of  miR-34c  in emphysematous lung, but this relationship was strongest for  SERPINE1  (p = 0.05).    Conclusion  Differences in miRNA expression are associated with emphysema severity in COPD patients.  MiR-34c  modulates expression of its putative target gene,  SERPINE1 ,  in vitro  in respiratory cell lines and  ex vivo  in emphysematous lung tissue.

MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression