Insights into the expression profiles and functions of circRNAs in a newborn hyperoxia‐induced rat bronchopulmonary dysplasia model

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease in preterm infants. Circular RNAs (circRNAs) are key regulators of various biological processes. The present study aimed to explore the biological roles of circRNAs in BPD pathogenesis. Methods:A newborn BPD rat model was developed to construct a circRNA library;Illumina deep sequencing (Illumina, San Diego, CA, USA) was used to reveal differential expression of circRNAs in the hyperoxia-induced BPD rat models. Sanger sequencing and a reverse transcription-polymerase chain reaction were performed to confirm circRNAs that may be related to BPD. After miRNA binding-site prediction, we constructed a network diagram of circRNA-competing endogenous RNAs (ceRNAs) related to transforming growth factor (TGF)-β and p53 pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.Results: In total, 256 differentially expressed circRNAs were detected between the hyperoxia group and the normoxia group. Of these circRNAs, 195 were up-regulated and 61 were down-regulated. The differences of circRNA distribution between the two groups were analyzed and six circRNAs were validated in the tissue samples. GO analysis indicated that 6519 target genes were enriched in cell location and biological processes. KEGG pathway enrichment analysis showed that circRNAs involved in 242 KEGG pathways. A network diagram of circRNA-ceRNA related to TGF-β and p53 pathways was constructed.Conclusions: CircRNAs are differentially expressed between the BPD model and control group. Many target genes of circRNAs are involved in the developmental process, which suggests that BPD may be associated with pathways including extracellular matrix-receptor interaction, vascular endothelial growth factor signaling and vascular smooth muscle contraction. K E Y W O R D S bronchopulmonary dysplasia, ceRNA, circRNA, deep sequencing, p53, TGF-β Cheng and Wu contributed equally to this work.

circRNA expression pattern and ceRNA network in the pathogenesis of aseptic loosening after total hip arthroplasty

“…CircRNAs were thought to be new star RNAs due to recent discovery of their diverse functions, vast abundance, and frequent tissue-specific expression, and played important roles in various cancers [19]. Further studies indicated that some circRNAs also played a important role in various types of non-cancer diseases and provided potential implications in accurate diagnosis and therapies [11,20]. While, only a few studies on the role of circRNAs in orthopedic disorders have been reported, and the contributions of circRNAs to pathogenesis of aseptic loosening remain basically unknown.…”

Research Article Differential expression of microRNAs in a hyperoxia-induced rat bronchopulmonary dysplasia model revealed by deep sequencing

“…Therefore, miRNAs can be used as biomarkers for certain diseases. In addition, our previous studies have demonstrated several novel circular RNAs, which may be associated with the pathophysiology of BPD (Cheng et al, 2020). To identify the miRNAs participated in the BPD, the expression profiles of the miRNAs were examined at 14 days.…”

“…We used a newborn rat model of BPD; 64 newborn Sprague-Dawley (SD) rats were randomly assigned to a hyperoxia group (exposure to 85% O 2 ) from day of birth or normoxia group (exposure to 21% O 2 ) based on our previous studies (Cheng et al, 2020). Foster rats in a hyperoxic chamber were rotated daily to avoid oxygen toxicity.…”

Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia

“…The potential regulatory lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA pathways are therefore constructed on the basis of their shared bridge miRNAs imprinted with miRNA responsive elements (MREs). Although primitive studies have illustrated the putative circRNA-mediated ceRNA network in the pathogenesis of rat BPD model ( Cheng et al, 2020 ), the comprehensive lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA networks supported by physiological evidence are largely unknown. Moreover, priming and preconditioning of CB-MNCs or UC-MSCs with different cytokines or growth factors are of great importance in cell therapy-based treatment of BPD.…”