The First Clinical Medical College of Lanzhou University, Lanzhou, People's Republic of China.
Department of Gerontal Respiratory Medicine, the First Hospital of Lanzhou University, Lanzhou, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2023 Mar 11;18:259-271. doi: 10.2147/COPD.S395492. eCollection 2023.
Chronic obstructive pulmonary disease (COPD) patients with osteoporosis (OP) usually experience more frequent exacerbations, worse quality of life, and heavier economic burden, however, few studies have investigated common molecular mechanisms of COPD and OP.
To explore the relationship between COPD and OP through bioinformatics analysis.
The miRNA microarray data of COPD and OP were retrieved from the Gene Expression Database (GEO), and the differentially expressed microRNAs (DEmiRNAs) were screened and the intersection was obtained. The Targetscan, miRDB, and miRWalk databases were used to predict the target genes of DEmiRNA, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R package clusterProfiler, the STRING database was used to analyze the target protein-protein interaction network (PPI) and screens to determine the core modules and core genes.
Two DEmiRNAs (miR-23a-5p, miR-194-3p) have been found in COPD and OP, which have predicted 76 and 114 target genes, respectively. GO functional annotations of miR-23a-5p were significantly enriched in CD40 signaling pathway, ubiquitin-conjugating enzyme activity, etc; KEGG pathways of miR-23a-5p were significantly enriched in ubiquitin-mediated proteolysis, folate biosynthesis, and regulation of actin cytoskeleton. GO function annotations of miR-194-3p were significantly enriched in T cell activation regulation, ubiquitin protein ligase activity, and DNA transcription factor binding; KEGG pathways of miR-194-3p were significantly enriched in cell adhesion molecules, intercellular tight junctions, and lysosomal pathway. PPI analysis found target coding proteins formed complex regulatory networks. Ten core genes (, , , , , , , , and ) were picked out among them, then we used the MCODE plugin found three core subnetworks.
Two identical DEmiRNAs (miR-23a-5p, miR-194-3p) exist in the peripheral blood of COPD and OP patients, which are important biomarkers for COPD patients with OP and may represent novel targets for diagnosis and treatment of COPD patients with OP.
患有骨质疏松症(OP)的慢性阻塞性肺疾病(COPD)患者通常会经历更频繁的恶化、更差的生活质量和更重的经济负担,然而,很少有研究探讨 COPD 和 OP 的常见分子机制。
通过生物信息学分析探讨 COPD 和 OP 之间的关系。
从基因表达数据库(GEO)中检索 COPD 和 OP 的 miRNA 微阵列数据,筛选差异表达的 microRNAs(DEmiRNAs)并获得交集。使用 Targetscan、miRDB 和 miRWalk 数据库预测 DEmiRNA 的靶基因,使用 R 包 clusterProfiler 进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,使用 STRING 数据库分析靶蛋白-蛋白相互作用网络(PPI)并筛选确定核心模块和核心基因。
在 COPD 和 OP 中发现了两个 DEmiRNAs(miR-23a-5p、miR-194-3p),分别预测出 76 个和 114 个靶基因。miR-23a-5p 的 GO 功能注释在 CD40 信号通路、泛素连接酶活性等方面显著富集;miR-23a-5p 的 KEGG 通路在泛素介导的蛋白水解、叶酸生物合成和肌动蛋白细胞骨架调节等方面显著富集。miR-194-3p 的 GO 功能注释在 T 细胞激活调节、泛素蛋白连接酶活性和 DNA 转录因子结合等方面显著富集;miR-194-3p 的 KEGG 通路在细胞黏附分子、细胞间紧密连接和溶酶体途径等方面显著富集。PPI 分析发现靶编码蛋白形成复杂的调控网络。在其中挑选出 10 个核心基因(、、、、、、、、和),然后使用 MCODE 插件发现了三个核心子网。
COPD 和 OP 患者外周血中存在两种相同的 DEmiRNAs(miR-23a-5p、miR-194-3p),它们是 COPD 合并 OP 患者的重要生物标志物,可能代表 COPD 合并 OP 患者诊断和治疗的新靶点。