Abstract：
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive.
METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out.
RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD.
CONCLUSIONS: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.
METHODS: A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out.
RESULTS: RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD.
CONCLUSIONS: RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.
摘要：
背景：慢性阻塞性肺疾病（COPD）的特点是发病率高，残疾,和全世界的死亡率。RNA结合蛋白（RBP）可能调控COPD患者氧化应激和炎症相关基因。单细胞转录组测序（scRNA-seq）为识别细胞间异质性和免疫细胞多样性提供了准确的工具。然而,RBPs在调节各种细胞中的作用，尤其是AT2细胞，仍然难以捉摸。
方法：采用scRNA-seq数据集（GSE173896）和从气道组织获得的大量RNA-seq数据集（GSE124180）进行数据挖掘。接下来,在COPD和对照患者中进行RNA-seq分析。差异表达基因（DEGs）使用倍数变化（FC≥1.5或≤1.5）和P值≤0.05的标准进行鉴定。最后,基因本体论（GO），京都基因和基因组百科全书（KEGG），并进行了选择性剪接鉴定分析。
结果：RBP基因在不同细胞群中表现出特定的表达模式，并参与AT2细胞的细胞增殖和线粒体功能障碍。作为RBP,AZGP1表达在scRNA-seq和RNA-seq数据集中均上调。它可能是一种候选免疫生物标志物，通过调节SAMD5，DNER的表达来调节AT2细胞增殖和粘附，从而调节COPD进展。DPYSL3、GBP5、GBP3和KCNJ2。此外，AZGP1调控COPD中的选择性剪接事件，特别是DDAH1和SFRP1，在COPD中具有重要意义。
结论：RBP基因AZGP1通过调节参与可变剪接的基因抑制COPD的上皮细胞增殖。
方法：采用scRNA-seq数据集（GSE173896）和从气道组织获得的大量RNA-seq数据集（GSE124180）进行数据挖掘。接下来,在COPD和对照患者中进行RNA-seq分析。差异表达基因（DEGs）使用倍数变化（FC≥1.5或≤1.5）和P值≤0.05的标准进行鉴定。最后,基因本体论（GO），京都基因和基因组百科全书（KEGG），并进行了选择性剪接鉴定分析。
结果：RBP基因在不同细胞群中表现出特定的表达模式，并参与AT2细胞的细胞增殖和线粒体功能障碍。作为RBP,AZGP1表达在scRNA-seq和RNA-seq数据集中均上调。它可能是一种候选免疫生物标志物，通过调节SAMD5，DNER的表达来调节AT2细胞增殖和粘附，从而调节COPD进展。DPYSL3、GBP5、GBP3和KCNJ2。此外，AZGP1调控COPD中的选择性剪接事件，特别是DDAH1和SFRP1，在COPD中具有重要意义。
结论：RBP基因AZGP1通过调节参与可变剪接的基因抑制COPD的上皮细胞增殖。
