Integrated Interaction Network of MicroRNA Target Genes in Keloid Scarring
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Integrated Interaction Network of MicroRNA Target Genes in Keloid Scarring Lechun Lyu1 · Yu Zhao2 · Hongquan Lu2 · Zijie Liu3 · Jiazhi Guo2 · Di Lu1,2 · Xiang Li4
© Springer Nature Switzerland AG 2019
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.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40291-018-0378-0) contains supplementary material, which is available to authorized users. * Di Lu [email protected] Jiazhi Guo [email protected] Xiang Li [email protected] 1
Technology Transfer Center, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, Yunnan, China
2
Biomedical Engineering Research Center, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming 650500, Yunnan, China
3
Department of Medical Laboratory Sciences, the First Affiliated Hospital of Kunming Medical University, Kunming, China
4
Department of Rehabilitation, Affiliated Hospital of Jining Medical University, Jining, China
Key Points The interaction network of microRNAs (miRNAs) and target genes plays a crucial role in the process of keloid formation. miRNA-21, miRNA-141-3p, miRNA-181a, and miRNA205 promote keloid fibroblast proliferation and reduce apoptosis via the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway. miRNA-637 and miRNA-1224 target the transforming growth factor (TGF)-β1/Smad3 signaling pathway, inhibit keloid fibroblast proliferation, and promote apopt
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