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

Savarimuthu Francis, Santiyagu M., Davidson, Morgan R., Tan, Maxine E., Wright, Casey M., Clarke, Belinda E., Duhig, Edwina E., Bowman, Rayleen V., Hayward, Nicholas K ., Fong, Kwun M. and Yang, Ian A. (2014) MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression. BMC Genomics, 15 1: . doi:10.1186/1471-2164-15-88


Author Savarimuthu Francis, Santiyagu M.
Davidson, Morgan R.
Tan, Maxine E.
Wright, Casey M.
Clarke, Belinda E.
Duhig, Edwina E.
Bowman, Rayleen V.
Hayward, Nicholas K .
Fong, Kwun M.
Yang, Ian A.
Title MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2014-01-30
Year available 2014
Sub-type Article (original research)
DOI 10.1186/1471-2164-15-88
Open Access Status DOI
Volume 15
Issue 1
Total pages 8
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
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.
Formatted 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 (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.
Keyword Chronic obstructive pulmonary disease
microRNA
miR-34c
Microarray
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article no.: 88

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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