Attenuation of miR-17∼92 Cluster in Bronchopulmonary Dysplasia.
BACKGROUND
Bronchopulmonary dysplasia remains a significant cause of neonatal morbidity; however, the identification of novel targets to predict or prevent the development of bronchopulmonary dysplasia remains elusive. Proper microRNA (miR)-17∼92 cluster is necessary for normal lung development, and alterations in expression are reported in other pulmonary diseases. The overall hypothesis for our work is that altered miR-17∼92 cluster expression contributes to the molecular pathogenesis of bronchopulmonary dysplasia.


OBJECTIVE
The current studies tested the hypothesis that alterations in miR-17∼92 cluster and DNA methyltransferase expression are present in bronchopulmonary dysplasia.


METHODS
miR-17∼92 cluster expression, promoter methylation, and DNA methyltransferase expression were determined in autopsy lung samples obtained from premature infants who died with bronchopulmonary dysplasia, or from term/near-term infants who died from nonrespiratory causes. Expression of miR-17∼92 cluster members miR-17 and -19b was measured in plasma samples collected in the first week of life from a separate cohort of preterm infants at a second institution in whom bronchopulmonary dysplasia was diagnosed subsequently.


RESULTS
Autopsy tissue data indicated that miR-17∼92 expression is significantly lower in bronchopulmonary dysplasia lungs and is inversely correlated with promoter methylation and DNA methyltransferase expression when compared with that of control subjects without bronchopulmonary dysplasia. Plasma sample analyses indicated that miR-17 and -19b expression was decreased in infants who subsequently developed bronchopulmonary dysplasia.


CONCLUSIONS
Our data are the first to demonstrate altered expression of the miR-17∼92 cluster in bronchopulmonary dysplasia. The consistency between our autopsy and plasma findings further support our working hypothesis that the miR-17∼92 cluster contributes to the molecular pathogenesis of bronchopulmonary dysplasia.
1 Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
Lynette K
LK
Rogers
2 Division of Neonatology and.
Mary
M
Robbins
3 Division of Pulmonary, Allergy, Critical Care, Sleep Medicine, College of Medicine; and.
Duaa
D
Dakhlallah
4 The Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, Ohio.
Zhaogang
Z
Yang
4 The Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, Ohio.
L James
LJ
Lee
5 Phylogeny, Inc., Powell, Ohio.
Madison
M
Mikhail
5 Phylogeny, Inc., Powell, Ohio.
Gerard
G
Nuovo
6 Department of Pediatrics, University of Rochester Medical Center, Rochester, New York; and.
Gloria S
GS
Pryhuber
7 Department of Epidemiology and.
Gerald
G
McGwin
3 Division of Pulmonary, Allergy, Critical Care, Sleep Medicine, College of Medicine; and.
Clay B
CB
Marsh
8 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Trent E
TE
Tipple
D001344:Autopsy; D001997:Bronchopulmonary Dysplasia / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding
C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D015254:DNA Modification Methylases
bronchopulmonary dysplasia; miR-17∼92 cluster; microRNA