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Published on: May 21, 2019
Integrated Interaction Network of MicroRNA Target Genes in Keloid Scarring
Lechun Lyu1, Yu Zhao2, Hongquan Lu2
1Technology Transfer Center, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
Abstract:
Keloids are a common dermal pathological disorder characterized by the excessive deposition of extracellular matrix components; however, the exact pathogenesis of the disease is still not clear. Studies increasingly suggest that microRNAs (miRNAs) can play a key role in the process of keloid scarring. In this study, the valuable miRNAs and target genes were screened and the interaction network was constructed. We also predicted target genes of reported miRNAs using TargetScan and miRTarBase software. Cytoscape 3.0.1 further showed the interaction network of miRNA and target genes. Among the various miRNAs involved in keloid pathogenesis, miRNA-21, miRNA-141-3p, miRNA-181a, and miRNA-205 were thought to up-regulate the proliferation and decrease apoptosis of keloid-derived fibroblasts through the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway. miRNA-637 and miRNA-1224 inhibited keloid fibroblasts proliferation and promoted apoptosis via the transforming growth factor (TGF)-β1/Smad3 signaling pathway. miRNA-21 was also involved in mitochondrial-mediated apoptosis and miRNA-31 targeted vascular endothelial growth factor (VEGF) signaling pathway. miRNA-199a may be one key factor in the cell cycle checkpoint signal pathway of keloid-derived fibroblasts. It was also found that miRNA-29a and miRNA-196a mediated collagen metabolism. These pivotal miRNAs and regulatory processes further improve the data on the epigenetic mechanisms of keloids and provide hope for the use of small molecules in the treatment of keloids.
Insights
MicroRNAs (miRNAs) significantly influence keloid scarring by regulating fibroblast proliferation and apoptosis. Specific miRNAs target key pathways like PI3K/Akt/mTOR and TGF-β1, offering potential epigenetic targets for keloid treatment.
Area of Science:
- Dermatology
- Molecular Biology
- Epigenetics
Background:
- Keloids are characterized by excessive extracellular matrix deposition, but their pathogenesis remains unclear.
- MicroRNAs (miRNAs) are increasingly recognized for their role in keloid scar formation.
- Understanding miRNA involvement is crucial for developing novel keloid treatments.
Purpose of the Study:
- To identify key miRNAs and their target genes involved in keloid pathogenesis.
- To construct the interaction network of miRNAs and target genes.
- To elucidate the epigenetic mechanisms underlying keloid scarring.
Main Methods:
- Prediction of miRNA target genes using TargetScan and miRTarBase.
- Construction of miRNA-target gene interaction networks using Cytoscape 3.0.1.
- Analysis of miRNA roles in fibroblast proliferation, apoptosis, and collagen metabolism.
Main Results:
- Several miRNAs (e.g., miR-21, miR-141-3p) up-regulate fibroblast proliferation via the PI3K/Akt/mTOR pathway.
- Other miRNAs (e.g., miR-637, miR-1224) inhibit proliferation and promote apoptosis through the TGF-β1/Smad3 pathway.
- Specific miRNAs were linked to apoptosis, VEGF signaling, cell cycle, and collagen metabolism.
Conclusions:
- Pivotal miRNAs and their regulatory pathways are identified in keloid pathogenesis.
- These findings enhance understanding of keloid epigenetic mechanisms.
- The study provides a basis for developing small molecule therapies targeting specific miRNAs for keloid treatment.
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