Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma / 医学前沿
Frontiers of Medicine
; (4): 1186-1203, 2023.
Article
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| ID: wpr-1010815
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WPRO
ABSTRACT
Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
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Base de datos:
WPRIM
Asunto principal:
Células Madre Neoplásicas
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Neoplasias de la Tiroides
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Factores de Transcripción TFIII
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Línea Celular Tumoral
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Proliferación Celular
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Transición Epitelial-Mesenquimal
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Células Madre Mesenquimatosas
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Vesículas Extracelulares
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Ratones Desnudos
Límite:
Animals
Idioma:
En
Revista:
Frontiers of Medicine
Año:
2023
Tipo del documento:
Article