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. 2020 Jul 3:2020:5156304.
doi: 10.1155/2020/5156304. eCollection 2020.

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

Chan Li  1 , Zeyu Zhang  2 , Qian Xu  3 , Ruizheng Shi  1
Affiliations

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

Chan Li et al. Biomed Res Int. .

Abstract

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
(a) Volcano plot of DEGs in IPAH. Green represents downregulated DEGs; red represents upregulated DEGs; and black represents no difference. (b) Heat map of the DEGs in IPAH compared with normal controls. Red represents greater expression and green represents less expression. (c) Volcano plot of DEMIs in IPAH. DEG: differentially expressed gene; IPAH: idiopathic pulmonary arterial hypertension; DEMI: differentially expressed miRNA.
Figure 2
Figure 2
The top 10 enriched Gene Ontology terms in biological process (a), cellular component (b), molecular function (c) and enriched Kyoto Encyclopedia of Genes and Genomes pathway (d) of DEGs. DEG: differentially expressed gene.
Figure 3
Figure 3
Protein-protein interaction network analysis (a) and hub genes (b) identified by Cytoscape.
Figure 4
Figure 4
DEMI-DEG network. Rhombus represents miRNA while rectangle represents mRNA. DEG: differentially expressed gene; DEMI: differentially expressed miRNA.
See this image and copyright information in PMC

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