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.
Children's Medical Center of Guangming New District Medical Group, Shenzhen, China.
J Gene Med. 2020 May;22(5):e3163. doi: 10.1002/jgm.3163. Epub 2020 Feb 7.
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.
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.
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.
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.
支气管肺发育不良（BPD）是一种严重的早产儿慢性肺部疾病。环状 RNA（circRNA）是多种生物学过程的关键调节因子。本研究旨在探讨 circRNA 在 BPD 发病机制中的生物学作用。
构建新生大鼠 BPD 模型构建 circRNA 文库；采用 Illumina 高通量测序（Illumina，圣地亚哥，CA，美国）揭示高氧诱导的 BPD 大鼠模型中 circRNA 的差异表达。采用 Sanger 测序和逆转录-聚合酶链反应（RT-PCR）验证可能与 BPD 相关的 circRNA。进行 miRNA 结合位点预测后，利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析构建 TGF-β 和 p53 通路相关的 circRNA-竞争性内源 RNA（ceRNA）网络图。
共检测到高氧组与常氧组之间 256 个差异表达的 circRNA。其中，195 个上调，61 个下调。分析两组间 circRNA 分布差异，在组织样本中验证 6 个 circRNA。GO 分析表明，6519 个靶基因在细胞位置和生物学过程中富集。KEGG 通路富集分析显示，circRNAs 涉及 242 个 KEGG 通路。构建了 TGF-β 和 p53 通路相关的 circRNA-ceRNA 网络图。
BPD 模型与对照组之间 circRNA 表达存在差异。circRNA 的许多靶基因参与发育过程，这表明 BPD 可能与细胞外基质-受体相互作用、血管内皮生长因子信号转导和血管平滑肌收缩等通路有关。
