Essential Genes and MiRNA–mRNA Network Contributing to the Pathogenesis of Idiopathic Pulmonary Arterial Hypertension

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Owing to its high fatality rate and narrow therapeutic options, identification of the pathogenic mechanisms IPAH becoming increasingly important. Methods: In our research, we utilized robust rank aggregation (RRA) method integrate four eligible (PAH) microarray datasets identified significant differentially expressed genes (DEGs) between normal samples. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathways were performed analyze their functions. The interaction network protein–protein (PPI) was constructed explore correlation these DEGs. functional modules hub further by weighted gene coexpression analysis (WGCNA). Moreover, miRNA dataset involved analyzed filter miRNAs (DE-miRNAs). Potential target screened DE-miRNAs predicted merged with DEGs miRNA–mRNA in IPAH. Some selected validated RT-PCR lung tissues from PAH animal model. Results: A total 260 DEGs, consisting 183 upregulated 77 downregulated identified, some those novel. Their molecular roles etiology remained vague. most crucial module mainly enriched biological processes, including leukocyte migration, cell chemotaxis, myeloid migration. Construction PPI showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, ADORA3 recognized as top 10 connectivity degrees. WGCNA five main pathogenesis Twelve nine identified. Among them, eight supposed be negatively regulated three DE-miRNAs, respectively. Conclusions: This study identifies key IPAH, well potential IPAH-related network. It provides deepening insights into vital clues seeking novel targets for