Circular RNAs expression profiles and bioinformatics analysis in bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) has long been considered the most challenging chronic lung disease for neonatologists and researchers due to its complex pathological mechanisms and difficulty in prediction. Growing evidence indicates that BPD is associated with the dysregulation of circular RNAs (circRNAs). Therefore, we aimed to explore the expression profiles of circRNAs and investigate the underlying molecular network associated with BPD.

Peripheral blood was collected from very-low-birth-weight (VLBW) infants at 5-8 days of life to extract PBMCs. Microarray analysis and qRT-PCR tests were performed to determine the differentially expressed circRNAs (DEcircRNAs) between BPD and non-BPD VLBW infants. Simultaneous analysis of GSE32472 was conducted to obtain differentially expressed mRNAs (DEmRNA) from BPD infants. The miRNAs were predicted by DEcircRNAs and DEmRNAs of upregulated, respectively, and then screened for overlapping ones. GO and KEGG analysis was performed following construction of the competing endogenous RNA regulatory network (ceRNA) for further investigation.

A total of 65 circRNAs (52 upregulated and 13 downregulated) were identified as DEcircRNAs between the two groups (FC >2.0 and p.adj <0.05). As a result, the ceRNA network was constructed based on three upregulated DEcircRNAs validated by qRT-PCR (hsa_circ_0007054, hsa_circ_0057950, and hsa_circ_0120151). Bioinformatics analysis indicated these DEcircRNAs participated in response to stimulus, IL-1 receptor activation, neutrophil activation, and metabolic pathways.

In VLBW infants with a high risk for developing BPD, the circRNA expression profiles in PBMCs were significantly altered in the early post-birth period, suggesting immune dysregulation caused by infection and inflammatory response already existed.