Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan 250012, China.
Shenzhen Research Institute of Shandong University, Shenzhen 518058, China.
Biosci Rep. 2020 Sep 30;40(9). doi: 10.1042/BSR20202346.
Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mitotic nuclear division, ATPase activity, and Herpes simplex virus one infection. Ten hub genes from three significant modules were ascertained by Cytoscape (CytoHubba). Gene set enrichment analysis (GSEA) plots showed that transcription elongation factor complex was the most significantly enriched gene set positively correlated with the PAH group. At the same time, solute proton symporter activity was the most significantly enriched gene set positively correlated with the control group. Correlation analysis between hub genes suggested that SMC4, TOP2A, SMC2, KIF11, KIF23, ANLN, ARHGAP11A, SMC3, SMC6 and RAD50 may involve in the pathogenesis of PAH. Then, the miRNA-target genes regulation network was performed to unveil the underlying complex association among them. Finally, RNA extracted from monocrotaline (MCT)-induced Rat-PAH model lung artery tissues were to conduct quantitative real-time PCR (qRT-PCR) to validate these hub genes. In conclusion, our study offers new evidence for the underlying molecular mechanisms of PAH as well as attractive targets for diagnosis and treatment of PAH.
肺动脉高压（PAH）是一种危及生命的慢性心肺疾病。然而，提供与 PAH 相关的基因表达谱的研究很少。为了确定与 PAH 相关的枢纽基因，我们研究了基因表达综合数据库（GEO）中的两个微阵列数据集。通过 limma 软件包鉴定出 150 个差异表达基因（DEGs）。DEGs 的富集基因本体论（GO）注释和京都基因与基因组百科全书（KEGG）途径主要包括有丝分裂核分裂、ATP 酶活性和单纯疱疹病毒 1 感染。通过 Cytoscape（CytoHubba）确定了三个显著模块中的 10 个枢纽基因。基因集富集分析（GSEA）图显示，转录伸长因子复合物是与 PAH 组最显著正相关的最显著富集基因集。同时，溶质质子转运体活性是与对照组最显著正相关的最显著富集基因集。枢纽基因之间的相关性分析表明，SMC4、TOP2A、SMC2、KIF11、KIF23、ANLN、ARHGAP11A、SMC3、SMC6 和 RAD50 可能参与 PAH 的发病机制。然后，进行了 miRNA 靶基因调控网络分析，以揭示它们之间潜在的复杂关联。最后，对野百合碱（MCT）诱导的大鼠 PAH 模型肺动脉组织提取的 RNA 进行定量实时 PCR（qRT-PCR）验证这些枢纽基因。总之，我们的研究为 PAH 的潜在分子机制提供了新的证据，并为 PAH 的诊断和治疗提供了有吸引力的靶点。
