MicroRNA dysregulation in the heart and lung of infants with bronchopulmonary dysplasia

Background and Objectives: Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth, resulting in significant morbidity and mortality. Recent studies have suggested that microRNA (miRNA) dysregulation is involved in the pathogenesis of BPD and may serve as biomarkers for early detection. We conducted a directed search for dysregulated miRNAs in lung and heart autopsy samples of infants with histologic BPD. Methods: We used archived lung and heart samples from BPD (13 lung, 6 heart) and control (24 lung, 5 heart) subjects. To measure miRNA expression, RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue specimens then reverse-transcribed, labeled, and hybridized to miRNA microarrays. The microarrays were scanned, and data were quantile normalized. Statistical analysis with a moderated t-test and control of the false discovery rate (5%) was used to compare normalized miRNA expression values between clinical categories. Results: With our set of 48 samples, 43 miRNAs had a significant difference in expression comparing BPD to non-BPD controls. Among the most statistically significant miRNAs, miR-378b, miRNA-184, miRNA-3667-5p, miRNA-3976, miRNA-4646-5p, and miRNA-7846-3p were all consistently upregulated in both the heart and lung tissues of BPD subjects. The cellular pathway predicted to be most affected by these miRNAs is the Hippo signaling pathway. Conclusions: This study identifies miRNAs that are similarly dysregulated in postmortem lung and heart samples in subjects with histologic BPD. These miRNAs may contribute to the pathogenesis of BPD, have potential as biomarkers, and may provide insight to novel approaches for diagnosis and treatment.