Integrative analysis of lncRNAs, miRNAs, and mRNAs-associated ceRNA network in a neonatal mouse model of bronchopulmonary dysplasia

Objective To elucidate the potential roles of the lncRNA-mediated competitive endogenous RNA (ceRNA) network in the pathogenesis of bronchopulmonary dysplasia (BPD), we performed an integrated bioinformatics analysis based on miRNA and mRNA microarray datasets between BPD and normal samples. Study design The mRNA and miRNA expression profiles of BPD were downloaded from the Gene Expression Omnibus (GEO) database to perform an integrated analysis. The limma package was used to identify differentially expressed genes (DEGs) and differentially expressed miRNA (DEmiRs), followed by functional enrichment analysis of DEGs. DEmiR-DEG and DEmiRNA-lncRNA interactions were predicted. Subsequently, the lncRNA-related ceRNA network was structured. Finally, a newborn BPD mouse model was established, and quantitative real-time PCR (qPCR) was used to validate the expression of the selected mRNAs, miRNAs, and lncRNAs. Results A total of 445 DEGs and 155 DEmiRs were obtained by comparing BPD samples and normal samples. Functional enrichment analysis showed that DEGs were primarily enriched in GO terms such as cell division and inflammatory response; and DEGs were mainly involved in the p53 signaling pathway. ThemiR17hg-miR-130b-3p-roundabout guidance receptor 2 (Robo2) andGM20455-miR-34a-5p-BMP/retinoic acid-inducible neural specific 1 (Brinp1) ceRNA axes were obtained by constructing the ceRNA network. In addition, the upregulation ofRobo2andmiR17hgwhile the downregulation ofmiR-130b-3p; as well as the upregulation ofBrinp1andGM20455but the downregulation ofmiR-34a-5pwere validated by qPCR. Conclusion ThemiR17hg-miR-130b-3p-Robo2andGM20455-miR-34a-5p-Brinp1axes may serve important role in the development of BPD. These findings might provide novel insight for a comprehensive understanding of molecular mechanisms in BPD, and genes in the ceRNA network might be considered as potential biomarkers and therapeutic targets against BPD.