Huang Yu-Xia, Li Fei, Liu Dong, Sun Yuan-Yuan, Zhao Qin-Hua, Jiang Rong, Wang Lan, Yuan Ping, Liu Jin-Ming, Wu Yue, Zhang Ji
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Radiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Ann Transl Med. 2021 Sep;9(18):1458. doi: 10.21037/atm-21-4342.
The role of microRNAs (miRNAs) in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) remains to be fully elucidated. This study evaluated the expression profile of miRNAs in the lung tissue of patients with SSc-PAH.
Lung tissue samples were collected from 3 SSc-PAH patients and 4 healthy controls. A small RNA high throughput sequence approach was used for screening the differentially expressed miRNAs in the lung tissue samples. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate 4 highly significant differentially expressed miRNAs. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for mRNAs were performed using the R package clusterProfiler software.
A total of 82 upregulated miRNAs and 35 downregulated miRNAs were detected in the lung tissues of patients with SSc-PAH compared with healthy controls. GO enrichment analysis demonstrated that the upregulated target genes were closely involved in biological processes such as nervous system development, anatomical structure morphogenesis, system development, cellular macromolecule metabolic processes, and cellular processes. The downregulated target genes were involved in the plasma membrane bound cell projection morphogenesis and the regulation of macromolecule metabolic processes. The KEGG enrichment analysis showed that the upregulated genes were associated with important pathways involved in cancer biology, and the target genes of the downregulated miRNAs were involved in axon guidance. High throughput sequencing and qRT-PCR revealed that hsa-miR-205-5p and hsa-miR-539-3p were differentially expressed in SSc-PAH tissue. The target genes of hsa-miR-205-5p and hsa-miR-539-3p, IRF1and ADCYAP1, respectively, were verified using the high throughput dataset GSE48149.
miRNAs may play an important role in the pathogenesis of SSc-PAH, and hsa-miR-205-5p and hsa-miR-539-3p may be potential therapeutic targets in patients with SSc-PAH.
微小RNA（miRNA）在系统性硬化症相关肺动脉高压（SSc-PAH）发病机制中的作用仍有待充分阐明。本研究评估了SSc-PAH患者肺组织中miRNA的表达谱。
收集3例SSc-PAH患者和4例健康对照者的肺组织样本。采用小RNA高通量测序方法筛选肺组织样本中差异表达的miRNA。运用实时定量逆转录聚合酶链反应（qRT-PCR）验证4个高度显著差异表达的miRNA。使用R包clusterProfiler软件对mRNA进行基因本体论（Gene Ontology）和京都基因与基因组百科全书（KEGG）富集分析。
与健康对照相比，在SSc-PAH患者的肺组织中总共检测到82个上调的miRNA和35个下调的miRNA。基因本体论富集分析表明，上调的靶基因密切参与神经系统发育、解剖结构形态发生、系统发育、细胞大分子代谢过程和细胞过程等生物学过程。下调的靶基因参与质膜结合细胞突起形态发生和大分子代谢过程的调节。KEGG富集分析显示，上调的基因与癌症生物学相关的重要通路有关，而下调的miRNA的靶基因参与轴突导向。高通量测序和qRT-PCR显示，hsa-miR-205-5p和hsa-miR-539-3p在SSc-PAH组织中差异表达。利用高通量数据集GSE48149分别验证了hsa-miR-205-5p和hsa-miR-539-3p的靶基因IRF1和ADCYAP1。
miRNA可能在SSc-PAH的发病机制中起重要作用，hsa-miR-205-5p和hsa-miR-539-3p可能是SSc-PAH患者潜在的治疗靶点。
