BACKGROUND Mastermind-like 1 (MAML1) is the main transcriptional co-activator of Notch signaling pathway. It plays essential roles in several pathways including MEF2C, p53, Nf-кB and Wnt/β-catenin. TWIST1 is known as a regulator of epithelial mesenchymal transition (EMT), which is considered as a primary step in promotion of tumor cell metastasis. Since concomitant expression of these genes was observed in tumors, our aim in this study was to elucidate the linkage between MAML1 and TWIST1 co-overexpression in esophageal squamous cell carcinoma (ESCC). RESULTS While MAML1 silencing significantly down-regulated TWIST1, its ectopic expression up-regulated TWIST1 expression in both mRNA and protein levels in KYSE-30 cells. Expression of mesenchymal markers was increased significantly after MAML1 and TWIST1 ectopic expression, while epithelial markers expression was significantly decreased after silencing of both genes. Concomitant protein expression of MAML1 and TWIST1 was significantly observed in ESCC patients. Enforced expression of TWIST1 had no impact on MAML1 gene expression in KYSE-30 cells. CONCLUSION The results clearly suggest transcriptional regulation of TWIST1 by MAML1 transcription factor in ESCC cells KYSE-30. Since TWIST1 is known as an EMT inducing marker, our results may revealed the mastermind behind TWIST1 function and introduced MAML1 as an upstream master regulator of TWIST1 and EMT in KYSE-30 cells.

中文翻译：

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MAML1通过上调EMT标记TWIST1促进ESCC侵略性。

背景技术Mastermind-like 1（MAML1）是Notch信号通路的主要转录共激活因子。它在包括MEF2C，p53，Nf-кB和Wnt /β-catenin在内的多种途径中起着至关重要的作用。TWIST1被称为上皮间质转化（EMT）的调节剂，被认为是促进肿瘤细胞转移的主要步骤。由于在肿瘤中观察到这些基因的同时表达，因此本研究的目的是阐明食管鳞状细胞癌（ESCC）中MAML1和TWIST1共过量表达之间的联系。结果尽管MAML1沉默显着下调了TWIST1，但其异位表达上调了KYSE-30细胞中mRNA和蛋白水平的TWIST1表达。MAML1和TWIST1异位表达后，间充质标记物的表达显着增加，两种基因沉默后，上皮标志物的表达明显降低。在ESCC患者中明显观察到了MAML1和TWIST1的伴随蛋白表达。TWIST1的强制表达对KYSE-30细胞中的MAML1基因表达没有影响。结论结果清楚地表明MAML1转录因子在ESCC细胞KYSE-30中对TWIST1的转录调控。由于TWIST1被称为EMT诱导标记，因此我们的结果可能揭示了TWIST1功能背后的策划者，并将MAML1引入了KYSE-30细胞中作为TWIST1和EMT的上游主调节剂。TWIST1的强制表达对KYSE-30细胞中的MAML1基因表达没有影响。结论结果清楚地表明MAML1转录因子在ESCC细胞KYSE-30中对TWIST1的转录调控。由于TWIST1被称为EMT诱导标记，因此我们的结果可能揭示了TWIST1功能背后的策划者，并将MAML1引入了KYSE-30细胞中作为TWIST1和EMT的上游主调节剂。TWIST1的强制表达对KYSE-30细胞中的MAML1基因表达没有影响。结论结果清楚地表明MAML1转录因子在ESCC细胞KYSE-30中对TWIST1的转录调控。由于TWIST1被称为EMT诱导标记，因此我们的结果可能揭示了TWIST1功能背后的策划者，并将MAML1引入了KYSE-30细胞中作为TWIST1和EMT的上游主调节剂。