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Exosomal miR-22-3p from Mesenchymal Stem Cells Inhibits the Epithelial-Mesenchymal Transition (EMT) of Melanoma Cells
Yong Chen1, Yuan Fang2,3, Li Li4
1Department of Plastic Surgery and Dermatology, The First Hospital of Changsha, 410005 Changsha, Hunan , China.
Background:
The mortality rate from melanoma has been rising and hence new therapeutic approaches for this disease have received extensive attention, especially the search for novel therapeutic targets. The aim of this study was to find new targets for the treatment of melanoma through a bioinformatics and experimental approach.
Methods:
First, we screened for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between melanoma and normal tissues using the TCGA-SKCM, GTEX, and GSE24996 datasets. Next, we identified epithelial-mesenchymal transition (EMT)-related DEGs and analyzed their expression levels and association with patient survival. The expression level of DEGs was then confirmed in normal human melanocytes and melanoma cells. Bioinformatics analysis was used to identify miRNAs that targeted the most highly expressed DEG, LGALS1, and their binding confirmed using dual luciferase. Enriched pathways for the LGALS1 target miR-22-3p were also analyzed. miR-22-3p was overexpressed in cells in order to investigate changes in cell activity and in related genes and proteins. Exosomes from human bone marrow mesenchymal stem cells (MSCs) were coated with miR-22-3p to examine its effect on EMT.
Results:
The expression levels of LGALS1, CPXM1, and APLNR were higher in melanoma than in normal tissues and were associated with worse patient survival. The differential expression of these genes was confirmed using normal human skin melanocytes (PIG1) and human melanoma cells (WM-266-4). LGALS1 was the most differentially expressed gene between WM-266-4 and PIG1 cells, and was also predicted to be a target for miR-22-3p. The results of dual luciferase experiments confirmed that miR-22-3p could bind to LGALS1. Following the overexpression of miR-22-3p in WM-266-4 cells, the cell viability decreased, the expression levels of LGALS1, VIM and SNAI2 decreased, the expression level of CDH1 increased, and cell apoptosis increased. Transfection of miR-22-3p using exosomes resulted in similar effects.
Conclusions:
We identified three genes (LGALS1, CPXM1, APLNR) that showed a high level of differential expression in melanoma. LGALS1 is a target for miR-22-3p binding and this can inhibit the EMT of melanoma cells, thereby preventing the development of melanoma. Moreover, exosomes secreted by MSCs can be loaded with miR-22-3p, thus regulating the EMT process in melanoma cells.
Insights
Researchers identified three key genes, LGALS1, CPXM1, and APLNR, overexpressed in melanoma. MiR-22-3p targets LGALS1, inhibiting melanoma cell epithelial-mesenchymal transition (EMT) and offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Genetics
- Biochemistry
Background:
- Melanoma mortality rates are increasing, necessitating novel therapeutic targets.
- Bioinformatics and experimental approaches are crucial for identifying new melanoma treatments.
Purpose of the Study:
- To identify novel therapeutic targets for melanoma using a combined bioinformatics and experimental strategy.
- To investigate the role of differentially expressed genes (DEGs) and microRNAs (miRNAs) in melanoma development.
Main Methods:
- Screened for DEGs and differentially expressed miRNAs (DEMs) using TCGA-SKCM, GTEX, and GSE24996 datasets.
- Identified and analyzed epithelial-mesenchymal transition (EMT)-related DEGs and their association with patient survival.
- Confirmed gene expression in melanocytes and melanoma cells, identified miRNA targets for LGALS1, and validated using dual luciferase assays and exosome transfection.
Main Results:
- LGALS1, CPXM1, and APLNR were significantly upregulated in melanoma tissues and associated with poorer survival.
- MiR-22-3p was confirmed to target LGALS1, leading to decreased cell viability, reduced EMT markers (LGALS1, VIM, SNAI2), increased CDH1 expression, and enhanced apoptosis.
- Exosome-mediated delivery of miR-22-3p mimicked these anti-melanoma effects.
Conclusions:
- LGALS1, CPXM1, and APLNR are identified as key differentially expressed genes in melanoma.
- MiR-22-3p inhibits melanoma cell EMT by targeting LGALS1, presenting a potential therapeutic avenue.
- Exosomes loaded with miR-22-3p can effectively regulate melanoma EMT, suggesting a novel drug delivery system.
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