Identification of Differentially Expressed Genes Associated with Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Approaches

2021 ◽  
Vol 28 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Enfa Zhao ◽  
Hang Xie ◽  
Yushun Zhang
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Differentially Expressed Genes ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Differentially Expressed ◽  
Pulmonary Arterial

scholarly journals Comprehensive Analyses of miRNA-mRNA Network and Potential Drugs in Idiopathic Pulmonary Arterial Hypertension

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chan Li ◽  
Zeyu Zhang ◽  
Qian Xu ◽  
Ruizheng Shi
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Pulmonary Arterial

Introduction. Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiopulmonary disease with a relatively low survival rate. Moreover, the pathogenesis of IPAH has not been fully recognized. Thus, comprehensive analyses of miRNA-mRNA network and potential drugs in IPAH are urgent requirements. Methods. Microarray datasets of mRNA and microRNA (miRNA) in IPAH were searched and downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMIs) were identified. Then, the DEMI-DEG network was conducted with associated comprehensive analyses including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis, while potential drugs targeting hub genes were investigated using L1000 platform. Results. 30 DEGs and 6 DEMIs were identified in the lung tissue of IPAH. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in antimicrobial humoral response and African trypanosomiasis, respectively. The DEMI-DEG network was conducted subsequently with 4 DEMIs (hsa-miR-34b-5p, hsa-miR-26b-5p, hsa-miR-205-5p, and hsa-miR-199a-3p) and 16 DEGs, among which 5 DEGs (AQP9, SPP1, END1, VCAM1, and SAA1) were included in the top 10 hub genes of the PPI network. Nimodipine was identified with the highest CMap connectivity score in L1000 platform. Conclusion. Our study conducted a miRNA-mRNA network and identified 4 miRNAs as well as 5 mRNAs which may play important roles in the pathogenesis of IPAH. Moreover, we provided a new insight for future therapies by predicting potential drugs targeting hub genes.

scholarly journals Essential genes and miRNA-mRNA network contributing to the pathogenesis of idiopathic pulmonary arterial hypertension

2020 ◽  
Author(s):  
Shengyu Hao ◽  
Pan Jiang ◽  
Liang Xie ◽  
Guiling Xiang ◽  
Zilong Liu ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Functional Module ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Leukocyte Migration ◽  
Differentially Expressed ◽  
Functional Modules ◽  
Hub Genes ◽  
Pulmonary Arterial

Abstract 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 of IPAH is becoming increasingly important.Methods: In our research, we utilized the Robust Rank Aggregating (RRA) method to integrate four eligible PAH microarray datasets and identified the significant differentially expressed genes (DEGs) between IPAH and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to analyze their functions. The interaction network of protein-protein internet (PPI) was constructed to explore the correlation between these DEGs. The functional modules and hub genes were further identified by the weighted gene coexpression network analysis (WGCNA). Moreover, a miRNA microarray dataset was involved and analyzed to filter differentially expressed miRNA (DE-miRNAs). Potential target genes of screened DE-miRNAs were predicted and merged with DEGs to explore a miRNA-mRNA network in IPAH. Some hub genes were selected and validated by RT-PCR in lung tissues from PAH animal model.Results: A total of 260 DEGs, consisting of 183 upregulated and 77 down-regulated significant DEGs were identified, and some of those genes were novel. Their molecular roles in the etiology of IPAH remained vague. The most crucial functional module involved in IPAH mainly enriched in biological processes, including leukocyte migration, cell chemotaxis, and myeloid leukocyte migration. Construction and analysis of the PPI network showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, and ADORA3 were recognized as top10 hub genes with high connectivity degrees. WGCNA further identified five main functional modules involved in the pathogenesis of IPAH. 12 upregulated DE-miRNAs and 9 downregulated DE-miRNAs were identified. Among them, four downregulated DEGs, and eight upregulated DEGs were supposed to be negatively regulated by three upregulated DE-miRNAs, and three downregulated DE-miRNAs, respectively.Conclusions: This study identifies some key and functional coexpression modules involved in IPAH, as well as a potential IPAH-related miRNA-mRNA regulated network. It provides deepening insights into the molecular mechanisms and provides vital clues in seeking novel therapeutic targets for IPAH.

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