%0 Journal Article %A Santiyagu Savarimuthu Francis %A Morgan Davidson %A Rayleen Bowman %A Nicholas Hayward %A Kwun Fong %A Ian Yang %T Dysregulated miRNAs and their predicted mRNA targets in emphysematous lungs %D 2011 %J European Respiratory Journal %P 1705 %V 38 %N Suppl 55 %X There is increasing recognition of the importance of microRNAs (miRNAs) as short non-coding RNAs that post-transcriptionally regulate gene expression. Identifying the role of miRNAs in COPD would enable better understanding of disease pathogenesis and use as biomarkers for diagnostic purposes or therapeutic targets. Our aims were i) to identify miRNAs dysregulated in mild and moderate emphysema, and ii) to identify mRNAs modulated by miR-34c-5p in BEAS-2B and HFL cell lines.Methods: i) miRNA microarray profiling (Agilent Human miRNA profiler G4470 V1.0) was performed on 29 non-tumour lung tissues obtained from The Prince Charles Hospital tissue bank. Patients were classified as mild (n=9) and moderate (n=20) emphysema according to lung function measurements (KCO and FEV1). Technical validation was performed on the selected miRNAs using quantitative real-time PCR. ii) Genomic mRNA expression changes from transient transfection of miR-34c-5p (candidate miRNA) in BEAS-2B and HFL cells were measured using Illumina HumanHT-12 V3 arrays.Results: COPD patients had mean (SD) age 68 (6) years, FEV1 72 (17)% predicted and KCO 70 (10)% predicted. Five miRNAs were identified (p<0.01) as differentially expressed in non-tumour lung tissues in mild vs moderate emphysema patients. Upregulation of miR-34c-5p in respiratory cell lines down-regulated predicted mRNAs.Conclusions: We have shown that miRNAs are associated with COPD severity and modulate expression of their predicted mRNAs.Support: NHMRC Biomedical Scholarship (SF), NHMRC Career Development Award (IY), The Prince Charles Hospital Foundation, Australian Lung Foundation/Boehringer Ingelheim COPD Research Fellowship. %U