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Updated: Jun 26, 2025

Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
Identifying the miRNA-gene networks contributes to exploring paravertebral muscle degeneration's underlying
Yongjin Li1,2, Wei Wang1, Chao Kong1
1Department of Orthopedics, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, China.
Abstract:
Low back pain (LBP) is a worldwide problem with public health. Paravertebral muscle degeneration (PMD) is believed to be associated with LBP. Increasing evidence has demonstrated that microRNA (miRNA)-mRNA signaling networks have been implicated in the pathophysiology of diseases. Research suggests that cell death, oxidative stress, inflammatory and immune response, and extracellular matrix (ECM) metabolism are the pathogenesis of PMD; however, the miRNA-mRNA mediated the pathological process of PMD remains elusive. RNA sequencing (RNA-seq) and single cell RNA-seq (scRNA-seq) are invaluable tools for uncovering the functional biology underlying these miRNA and gene expression changes. Using scRNA-seq, we show that multiple immunocytes are presented during PMD, revealing that they may have been implicated with PMD. Additionally, using RNA-seq, we identified 76 differentially expressed genes (DEGs) and 106 differentially expressed miRNAs (DEMs), among which IL-24 and CCDC63 were the top upregulated and downregulated genes in PMD. Comprehensive bioinformatics analyses, including Venn diagrams, differential expression, functional enrichment, and protein-protein interaction analysis, were then conducted to identify six ferroptosis-related DEGs, two oxidative stress-related DEGs, eleven immunity-related DEGs, five ECM-related DEGs, among which AKR1C2/AKR1C3/SIRT1/ALB/IL-24 belong to inflammatory genes. Furthermore, 67 DEMs were predicted to be upstream miRNAs of 25 key DEGs by merging RNA-seq, TargetScan, and mirDIP databases. Finally, a miRNA-gene network was constructed using Cytoscape software and an alluvial plot. ROC curve analysis unveiled multiple key DEGs with the high clinical diagnostic value, providing novel approaches for diagnosing and treating PMD diseases.
Insights
Low back pain (LBP) is linked to paravertebral muscle degeneration (PMD). This study identifies key microRNA (miRNA)-mRNA networks and immune cell involvement in PMD pathogenesis, offering potential diagnostic and therapeutic targets.
Area of Science:
- Biomedical research
- Molecular biology
- Genomics
Background:
- Low back pain (LBP) is a significant global health issue.
- Paravertebral muscle degeneration (PMD) is associated with LBP, involving processes like cell death, oxidative stress, inflammation, and extracellular matrix (ECM) metabolism.
- The specific miRNA-mRNA networks mediating PMD pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the role of miRNA-mRNA signaling networks in PMD.
- To identify key genes and miRNAs involved in PMD pathophysiology.
- To explore potential diagnostic and therapeutic strategies for PMD.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) to identify immune cell infiltration in PMD.
- RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs) and miRNAs (DEMs).
- Bioinformatics analyses including differential expression, functional enrichment, protein-protein interaction, and miRNA-gene network construction.
Main Results:
- scRNA-seq revealed the presence of multiple immunocytes in PMD.
- RNA-seq identified 76 DEGs and 106 DEMs, with IL-24 and CCDC63 as top upregulated and downregulated genes, respectively.
- Bioinformatics analyses highlighted DEGs related to ferroptosis, oxidative stress, immunity, and ECM metabolism, with several identified as inflammatory genes. A miRNA-gene network was constructed, and ROC analysis indicated high diagnostic value for key DEGs.
Conclusions:
- This study elucidates the miRNA-mRNA mediated pathological processes in PMD.
- Identified DEGs and DEMs, along with immune cell involvement, provide novel insights into PMD.
- The findings offer potential biomarkers for diagnosing PMD and suggest new therapeutic avenues.
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