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MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression
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MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression
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Journal Article
MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression
2014
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V
Subject
/ Aged
/ Animal Genetics and Genomics
/ Arrays
/ Asthma
/ Biomedical and Life Sciences
/ Chronic obstructive pulmonary disease
/ Female
/ Hepatocyte Nuclear Factor 4 - genetics
/ Hepatocyte Nuclear Factor 4 - metabolism
/ Humans
/ Male
/ Microbial Genetics and Genomics
/ Oligonucleotide Array Sequence Analysis
/ Plasminogen Activator Inhibitor 1 - genetics
/ Plasminogen Activator Inhibitor 1 - metabolism
/ Pulmonary Disease, Chronic Obstructive - genetics
/ Pulmonary Disease, Chronic Obstructive - metabolism
/ Pulmonary Disease, Chronic Obstructive - pathology
/ Studies
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