Open Access Research article

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

Santiyagu M Savarimuthu Francis12*, Morgan R Davidson12, Maxine E Tan2, Casey M Wright12, Belinda E Clarke3, Edwina E Duhig3, Rayleen V Bowman12, Nicholas K Hayward24, Kwun M Fong12 and Ian A Yang12

Author Affiliations

1 Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD 4032, Australia

2 School of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia

3 Department of Anatomical Pathology, The Prince Charles Hospital, Brisbane, QLD 4032, Australia

4 Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia

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BMC Genomics 2014, 15:88  doi:10.1186/1471-2164-15-88

Published: 30 January 2014

Abstract

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, FEV1 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 (pā€‰<ā€‰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 (pā€‰=ā€‰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.

Keywords:
Chronic obstructive pulmonary disease; microRNA; miR-34c; Microarray