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.

中文翻译：

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特发性肺动脉高压中 miRNA-mRNA 网络和潜在药物的综合分析。

简介。特发性肺动脉高压（IPAH）是一种严重的心肺疾病，生存率相对较低。此外，IPAH的发病机制尚未得到充分认识。因此，迫切需要对 IPAH 中的 miRNA-mRNA 网络和潜在药物进行综合分析。方法. 从 Gene Expression Omnibus (GEO) 搜索并下载 IPAH 中 mRNA 和 microRNA (miRNA) 的微阵列数据集。鉴定了差异表达基因（DEGs）和差异表达miRNAs（DEMIs）。然后，对 DEMI-DEG 网络进行了相关的综合分析，包括基因本体 (GO) 分析、京都基因和基因组百科全书 (KEGG) 通路富集分析和蛋白质-蛋白质相互作用 (PPI) 网络分析，而潜在的药物靶向中心使用L1000平台研究基因。结果. 在 IPAH 的肺组织中鉴定出 30 个 DEGs 和 6 个 DEMIs。GO 和 KEGG 通路分析显示，这些 DEG 主要分别富含抗菌体液反应和非洲锥虫病。随后使用 4 个 DEMI（hsa-miR-34b-5p、hsa-miR-26b-5p、hsa-miR-205-5p 和 hsa-miR-199a-3p）和 16 个 DEG 进行 DEMI-DEG 网络，其中其中 5 个 DEG（AQP9、SPP1、END1、VCAM1 和 SAA1）被包含在 PPI 网络的前 10 个中心基因中。尼莫地平在 L1000 平台中被确定为具有最高的 CMap 连接分数。结论. 我们的研究进行了一个 miRNA-mRNA 网络，并确定了 4 个 miRNA 和 5 个可能在 IPAH 发病机制中起重要作用的 mRNA。此外，我们通过预测靶向中心基因的潜在药物，为未来的治疗提供了新的见解。