Yang Ting, Xu Wenya, Zhao Jie, Chen Jie, Li Siguang, Lin Lingsang, Zhong Yi, Yang Zehua, Xie Tian, Ding Yipeng
Department of General Practice, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, Hainan, China.
Zayun Township Health Center, Qiongzhong Li and Miao Autonomous County, Haikou, Hainan, China.
Front Genet. 2024 Sep 3;15:1402856. doi: 10.3389/fgene.2024.1402856. eCollection 2024.
The chronic respiratory condition known as chronic obstructive pulmonary disease (COPD) was one of the main causes of death and disability worldwide. This study aimed to explore and elucidate new targets and molecular mechanisms of COPD by constructing competitive endogenous RNA (ceRNA) networks.
GSE38974 and GSE106986 were used to select DEGs in COPD samples and normal samples. Cytoscape software was used to construct and present protein-protein interaction (PPI) network, mRNA-miRNA co-expression network and ceRNA network. The CIBERSORT algorithm and the Lasso model were used to screen the immune infiltrating cells and hub genes associated with COPD, and the correlation between them was analyzed. COPD cell models were constructed and the expression level of ceRNA network factors mediated by hub gene was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
In this study, 852 differentially expressed genes were screened in the GSE38974 dataset, including 439 upregulated genes and 413 downregulated genes. Gene clustering analysis of PPI network results was performed using the Minimum Common Tumor Data Element (MCODE) in Cytoscape, and seven hub genes were screened using five algorithms in cytoHubba. CCL20 was verified as an important hub gene based on mRNA-miRNA co-expression network, GSE106986 database validation and the analysis of ROC curve results. Finally, we successfully constructed the circDTL-hsa-miR-330-3p-CCL20 network by Cytoscape. Immune infiltration analysis suggested that CCL20 can co-regulate immune cell migration and infiltration through chemokines CCL7 and CXCL3. experiments, the expression of circDTL and CCL20 was increased, while the expression of hsa-miR-330-3p was decreased in the COPD cell model.
By constructing the circDTL-hsa-miR-330-3p-CCL20 network, this study contributes to a better understanding of the molecular mechanism of COPD development, which also provides important clues for the development of new therapeutic strategies and drug targets.
慢性阻塞性肺疾病（COPD）这一慢性呼吸系统疾病是全球主要的死亡和致残原因之一。本研究旨在通过构建竞争性内源性RNA（ceRNA）网络来探索和阐明COPD的新靶点及分子机制。
利用GSE38974和GSE106986数据集筛选COPD样本和正常样本中的差异表达基因（DEGs）。使用Cytoscape软件构建并展示蛋白质-蛋白质相互作用（PPI）网络、mRNA- miRNA共表达网络和ceRNA网络。运用CIBERSORT算法和Lasso模型筛选与COPD相关的免疫浸润细胞和枢纽基因，并分析它们之间的相关性。构建COPD细胞模型，通过逆转录-定量聚合酶链反应（RT-qPCR）检测由枢纽基因介导的ceRNA网络因子的表达水平。
在本研究中，在GSE38974数据集中筛选出852个差异表达基因，其中439个上调基因和413个下调基因。使用Cytoscape中的最小共同肿瘤数据元素（MCODE）对PPI网络结果进行基因聚类分析，并在cytoHubba中使用五种算法筛选出七个枢纽基因。基于mRNA-miRNA共表达网络、GSE106986数据库验证以及ROC曲线结果分析，CCL20被确认为一个重要的枢纽基因。最后，我们通过Cytoscape成功构建了circDTL-hsa-miR-330-3p-CCL20网络。免疫浸润分析表明，CCL20可通过趋化因子CCL7和CXCL3共同调节免疫细胞迁移和浸润。在实验中，COPD细胞模型中circDTL和CCL20的表达增加，而hsa-miR-330-3p的表达降低。
通过构建circDTL-hsa-miR-330-3p-CCL20网络，本研究有助于更好地理解COPD发生发展的分子机制，也为开发新的治疗策略和药物靶点提供了重要线索。
