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The expression profiling of microRNA in systemic sclerosis-associated pulmonary arterial hypertension
Yu-Xia Huang1, Fei Li2, Dong Liu3
1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
MicroRNAs (miRNAs) are implicated in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). This study identified specific miRNAs, hsa-miR-205-5p and hsa-miR-539-3p, as potential therapeutic targets for SSc-PAH.
Area of Science:
- Pulmonary Hypertension Research
- Molecular Biology
- Genetics
Background:
- Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) pathogenesis is not fully understood.
- MicroRNAs (miRNAs) are increasingly recognized for their role in disease development.
- This study investigates miRNA expression in SSc-PAH lung tissue.
Purpose of the Study:
- To elucidate the role of microRNAs (miRNAs) in the pathogenesis of SSc-PAH.
- To identify differentially expressed miRNAs in lung tissue from SSc-PAH patients.
- To explore potential therapeutic targets for SSc-PAH.
Main Methods:
- Small RNA high-throughput sequencing of lung tissue from SSc-PAH patients and healthy controls.
- Validation of differentially expressed miRNAs using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).
- Gene Ontology (GO) and KEGG pathway enrichment analysis of target genes.
Main Results:
- Identified 82 upregulated and 35 downregulated miRNAs in SSc-PAH lung tissue.
- Upregulated miRNAs targeted genes involved in nervous system and cellular development.
- Downregulated miRNAs targeted genes involved in cell projection morphogenesis and axon guidance; hsa-miR-205-5p and hsa-miR-539-3p were significantly differentially expressed.
Conclusions:
- MicroRNAs play a significant role in SSc-PAH pathogenesis.
- hsa-miR-205-5p and hsa-miR-539-3p represent potential therapeutic targets for SSc-PAH treatment.
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