Hanrong Cheng1, Benqing Wu2, Lingwei Wang1, Tianyong Hu3, Zhuhui Deng3, Dongcai Li3. 1. Institute of Respiratory Diseases, Shenzhen People's Hospital; The First Affiliated Hospital of Southern University of Science and Technology; The Second Clinical Medical College of Jinan University, Shenzhen, China. 2. Children's Medical Center of Guangming New District Medical Group, Shenzhen, China. 3. Institute of ENT and Shenzhen Key Laboratory of ENT, Longgang ENT Hospital, Shenzhen, China.
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.
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 BPDrat 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 BPDrat 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.