Identification of Key Genes and miRNA-mRNA Regulatory Pathways in
Bronchopulmonary Dysplasia in Preterm Infants by Bioinformatics Methods
Abstract
Background: BPD remains a severe respiratory complication of preterm
infants in NICUs. However, its pathogenesis has been unclear.
Bioinformatics analysis, which can help us explore genetic alternations
and recognize latent diagnostic biomarkers, has recently promoted the
comprehension of the molecular mechanisms underlying disease occurrence
and development. Methods: In this study, we identified key genes and
miRNA-mRNA regulatory networks in BPD in preterm infants to elucidate
the pathogenesis of BPD. We downloaded and analyzed miRNA and gene
expression microarray datasets from the Gene Expression Omnibus database
(GEO). Differentially expressed miRNA (DEMs) and differentially
expressed genes (DEGs) were obtained through NetworkAnalyst. We
performed pathway enrichment analysis using the Database for Annotation,
Visualization and Integrated Discovery program (DAVID), Gene Ontology
(GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then we used
the STRING to establish protein–protein interactions and the Cytoscape
tool to establish miRNA–mRNA regulatory networks. Results: We
identified 19 significant DEMs and 140 and 33 significantly upregulated
and downregulated DEGs, respectively. Functional enrichment analysis
indicated that significant DEGs were associated with the antigen
processing and presentation, and B-cell receptor signaling pathways in
BPD. Key DEGs, such as CD19, CD79B, MS4A1, and FCGR2B were selected as
hub genes in PPI networks. Conclusions: In this study, we screened out
19 DEMs that might play important roles in the regulatory networks of
BPD. Higher expression of miRNAs such as miR-15b-5p, hsa-miR-32-5p,
miR-3613-3p, and miR-33a-5p and lower expression of miRNAs such as
miR-3960, miR-425-5p, and miR-3202 might be correlated with the process
of BPD.