Of mice and men: Correlations between microRNA-17~92 cluster expression and promoter methylation in severe bronchopulmonary dysplasia

Mary E. Robbins, Duaa Dakhlallah, Clay B. Marsh, Lynette K. Rogers, Trent E. Tipple*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

We previously demonstrated that decreased miR-17~92 cluster expression was 1) present in lungs from human infants who died with bronchopulmonary dysplasia (BPD); 2) inversely correlated with DNA methyltransferase (DNMT) expression and promoter methylation; and 3) correlated with a subsequent diagnosis of BPD at 36 wk gestational age. We tested the hypothesis that plasma miR-17 levels would be lowest in infants who ultimately develop severe BPD. Secondly, we utilized our well-characterized murine model of severe BPD that combines perinatal inflammation with postnatal hyperoxia to test the hypothesis that alterations in lung miR-17~92, DNMT, and promoter methylation in our model would mirror our findings in tissues from premature human infants. Plasma was obtained during the first 5 days of life from premature infants born ≤32 wk gestation. Lung tissues were harvested from mice exposed to maternal inflammation and neonatal hyperoxia for 14 days after birth. miR-17~92 cluster expression and DNA methyltransferase expression were measured by qRT-PCR, and promoter methylation was assessed by Methyl-Profiler assay. Plasma miR-17 levels are significantly lower in the first week of life in human infants who develop severe BPD compared with mild or moderate BPD. Data from our severe BPD murine model reveal that lung miR-17~92 cluster expression is significantly attenuated, and levels inversely correlated with DNMT expression and miR-17~92 cluster promoter methylation. Collectively, our data support a plausible role for epigenetically altered miR-17~92 cluster in the pathogenesis of severe BPD.

Original languageEnglish (US)
Pages (from-to)L981-L984
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number5
DOIs
StatePublished - 2016

Keywords

  • Bronchopulmonary dysplasia
  • DNMT
  • Methylation
  • MiR-17~92
  • MicroRNA

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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