Differential expression of long non‐coding RNAs in hyperoxia‐induced bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is a common complication of premature birth that seriously affects the survival rate and quality of life among preterm neonates. Long non-coding RNAs (lncRNAs) have been implicated in many human diseases. However, the role of lncRNAs in the pathogenesis of BPD remains poorly understood. Here, we exposed neonatal C57BL/6J mice to 95% concentrations of ambient oxygen and established a mouse lung injury model that mimicked human BPD. Next, we compared lncRNA and messenger RNA (mRNA) expression profiles between BPD and normal lung tissues using a high-throughput mouse lncRNA + mRNA array system. Compared with the control group, 882 lncRNAs were upregulated, and 887 lncRNAs were downregulated in BPD lung tissues. We validated some candidate BPD-associated lncRNAs by real-time quantitative reverse-transcription polymerase chain reaction analysis in eight pairs of BPD and normal lung tissues. Gene ontology, pathway and bioinformatics analyses revealed that a downregulated lncRNA, namely AK033210, associated with tenascin C may be involved in the pathogenesis of BPD. To the best of our knowledge, our study is the first to reveal differential lncRNA expression in BPD, which provides a foundation for further understanding of the molecular mechanism of BPD development. Copyright © 2016 John Wiley & Sons, Ltd.

Can We Understand the Pathobiology of Bronchopulmonary Dysplasia?

“…Subsequently, however, genome wide association studies were unable to identify single nucleotide polymorphisms significantly associated with an increased risk of BPD 165, 166 . Additional screens to detect epigenetic marks 167 and changes in long non-coding RNA 168 , have recently been performed, and others such as proteomic and metabolomic screens, have not yet been undertaken. Although these advances in high throughput, ‘omic’ technologies can yield vast amounts of data, heterogeneity in the diseased population and the presence of multiple confounding factors can limit the power to differentiate true signals from background noise.…”

Changes in the Composition of the Gut Microbiota and the Blood Transcriptome in Preterm Infants at Less than 29 Weeks Gestation Diagnosed with Bronchopulmonary Dysplasia

“…The association of rare variants with BPD has been evaluated through multiple exome sequencing studies, which have suggested a role for kinase A- and mitogen-activated protein (MAP) kinase-related pathways in BPD (13–15). To date, microarray-based gene expression studies of BPD have been performed on both blood and lung tissue samples collected from infants and from animal models and have identified several thousand genes as potentially being differentially expressed in BPD (16–19). These studies reported that pathways involved in the inflammatory response are downregulated in BPD infants, while pathways related to the cell cycle are upregulated (18).…”

Long non‐coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB

“…[46][47][48] In a recent report, researchers have screened differentially expressed lncRNAs in a hyperoxia-induced neonatal mouse BPD model, indicating that lncRNAs might participate in BPD development. 49 MALAT1, one lncRNA, is involved in several physiopathological process including angiogenesis, 50 diabetes progression, 51 tumour progression, 52 cardiovascular remodelling 53 and tissue inflammation. 19 It can play multiple roles, like promoting protein localization, acting as a competing endogenous RNA, or regulating protein activity, gene transcription and epigenetic changes.…”