Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Biomed Res Int. 2020 Jul 3;2020:5156304. doi: 10.1155/2020/5156304. eCollection 2020.
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.
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.
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.
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.
特发性肺动脉高压（IPAH）是一种严重的心肺疾病，其存活率相对较低。此外，IPA 的发病机制尚未完全阐明。因此，IPA 中 miRNA-mRNA 网络和潜在药物的综合分析是当务之急。
从基因表达综合数据库（GEO）中搜索并下载 IPAH 的 mRNA 和 microRNA（miRNA）微阵列数据集。鉴定差异表达基因（DEGs）和差异表达 microRNAs（DEMIs）。然后，进行 DEMI-DEG 网络分析，包括基因本体论（GO）分析、京都基因与基因组百科全书（KEGG）通路富集分析和蛋白质-蛋白质相互作用（PPI）网络分析，同时利用 L1000 平台研究针对枢纽基因的潜在药物。
在 IPAH 患者的肺组织中鉴定出 30 个 DEGs 和 6 个 DEMIs。GO 和 KEGG 通路分析表明，这些 DEGs 主要富集在抗菌体液反应和非洲锥虫病中。随后进行了 DEMI-DEG 网络分析，其中包含 4 个 DEMIs（hsa-miR-34b-5p、hsa-miR-26b-5p、hsa-miR-205-5p 和 hsa-miR-199a-3p）和 16 个 DEGs，其中 5 个 DEGs（AQP9、SPP1、END1、VCAM1 和 SAA1）包含在 PPI 网络的前 10 个枢纽基因中。在 L1000 平台中，尼莫地平的 CMap 连接得分最高。
本研究进行了 miRNA-mRNA 网络分析，鉴定了 4 个 miRNA 和 5 个可能在 IPAH 发病机制中起重要作用的 mRNA。此外，通过预测针对枢纽基因的潜在药物，为未来的治疗提供了新的思路。
