通过生物信息学预测，我们发现GTF2I和FAT1在甲状腺癌（TC）中被下调。此外，Pearson相关系数显示，GTF2I的表达与FAT1的表达呈正相关。因此，在本研究中，我们选择了它们，评估了骨髓间充质干细胞衍生的外泌体（BMSDs-EVs）富集的GTF2I对TC中上皮-间充质转化（EMT）和干细胞性维持的影响。我们验证了GTF2I和FAT1在TC细胞系中的低表达。人工过表达的GTF2I和FAT1增强了TC细胞的恶性表型、EMT和干细胞性维持。机制研究显示，GTF2I结合到FAT1的启动子区域，并因此上调了其表达。MSC-EVs可以将GTF2I转运到TPC-1细胞中，GTF2I通过增加FAT1的表达并促进FAT1介导的CDK4/FOXM1的下调，抑制了TC的恶性表型、EMT和干细胞性维持。体内实验证实了沉默GTF2I加速裸鼠中肿瘤的生长。综上所述，我们的研究结果表明，通过MSC-EVs传递的GTF2I通过FAT1/CDK4/FOXM1轴发挥抗肿瘤效应，并且可能作为TC治疗的有希望的生物标志物。© 2023. 高等教育出版社。

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.© 2023. Higher Education Press.