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

Abstract

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. The miR17hg-miR-130b-3p-roundabout guidance receptor 2 (Robo2) and GM20455-miR-34a-5p-BMP/retinoic acid-inducible neural specific 1 (Brinp1) ceRNA axes were obtained by constructing the ceRNA network. In addition, the upregulation of Robo2 and miR17hg while the downregulation of miR-130b-3p; as well as the upregulation of Brinp1 and GM20455 but the downregulation of miR-34a-5p were validated by qPCR.

Conclusion

The miR17hg-miR-130b-3p-Robo2 and GM20455-miR-34a-5p-Brinp1 axes 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.

Keywords:

• Bronchopulmonary dysplasia
• hyperoxia
• microarray
• competing endogenous RNA
• microRNA
• long non-coding RNA

Ethical approval

The study was approved by the Institutional Animal Care and Use Committee of Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, and all the processes were done in accordance with the institutional guidelines for animal care.

Authors’ contributions

Conception and design of the research: XZ; acquisition of data: YD; analysis and interpretation of data: XZ, YD; statistical analysis: XZ, YD; drafting the manuscript: XZ, YD; revision of manuscript for important intellectual content: XZ. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article.