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Identification of the Core MicroRNAs and Potential Molecular Mechanismsin Sarcoidosis Using Bioinformatics Analysis
Yuan Cao1, Hua Zhang2, Lulu Zheng1
1Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an, China.
Abstract:
Sarcoidosis is a systemic heterogeneous inflammatory disease; however, the etiology and pathogenesis of sarcoidosis are still unknown. Herein, we investigated the core microRNAs and potential molecular mechanisms in sarcoidosis. The DE-miRNAs were diagnosed using the LIMMA software package. DIANA-mirPath was employed to perform pathway and GO enrichment analysis of the DE-miRNAs. PPI networks and miRNA-target gene regulatory networks were used to obtain insight into the actions of DE-miRNAs. Expression of the hub genes along with miRNAs was validated in clinical specimens. Overall, 266 DE-miRNAs were screened. Among these DE-miRNAs, hsa-miR-144, hsa-miR-126, as well as hsa-miR-106a were the upmost upregulated miRNAs; hsa-miR-151-3p, hsa-miR-320d, and hsa-miR-324-3p were the top downregulated miRNAs. NR3C1, ZBTB7A, NUFIP2, BZW1, ERGIC2, and VEGFA were mapped as the most targeted hub genes in the upregulation of miRNAs, and MCL1 and SAE1 were the most targeted hub genes in the downregulation of miRNA. VEGFA and NR3C1 were selected and potentially modulated by hsa-miR-20b, hsa-miR-126, and hsa-miR-106a. In sarcoidosis pathological tissue, hsa-miR-126 was highly expressed, and VEGFA and NR3C1 were overexpressed. In conclusion, our results revealed the dysregulation of hsa-miR-126 and a potential regulatory mechanism for pathogenesis in sarcoidosis.
Insights
This study identifies key microRNAs (miRNAs) involved in sarcoidosis pathogenesis. Dysregulation of hsa-miR-126 and its target genes VEGFA and NR3C1 may play a crucial role in sarcoidosis development.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Sarcoidosis is a systemic inflammatory disease with unknown etiology and pathogenesis.
- Understanding the molecular mechanisms, particularly the role of microRNAs (miRNAs), is crucial for unraveling sarcoidosis pathology.
Purpose of the Study:
- To investigate core microRNAs (miRNAs) and potential molecular mechanisms in sarcoidosis.
- To identify differentially expressed miRNAs (DE-miRNAs) and their target genes in sarcoidosis.
Main Methods:
- Differentially expressed miRNAs (DE-miRNAs) were identified using LIMMA software.
- Pathway and Gene Ontology (GO) enrichment analyses were performed using DIANA-mirPath.
- Protein-protein interaction (PPI) and miRNA-target gene regulatory networks were constructed.
- Hub genes and miRNA expression were validated in clinical specimens.
Main Results:
- A total of 266 DE-miRNAs were screened.
- Key upregulated miRNAs include hsa-miR-144, hsa-miR-126, and hsa-miR-106a.
- Key downregulated miRNAs include hsa-miR-151-3p, hsa-miR-320d, and hsa-miR-324-3p.
- Hub genes NR3C1, VEGFA, ZBTB7A, NUFIP2, BZW1, and ERGIC2 were identified.
- hsa-miR-126 was highly expressed in sarcoidosis tissue, along with its targets VEGFA and NR3C1.
Conclusions:
- The study reveals significant dysregulation of specific miRNAs in sarcoidosis.
- hsa-miR-126, VEGFA, and NR3C1 are identified as potential key players in sarcoidosis pathogenesis.
- These findings suggest a novel regulatory mechanism involving hsa-miR-126 in sarcoidosis development.
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