Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.

中文翻译：

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早期生长反应1调节双特异性蛋白磷酸酶1并抑制舌鳞状细胞癌的细胞迁移和侵袭。

口腔鳞状细胞癌（OSCC）是头颈部最常见的恶性肿瘤之一，其中舌鳞状细胞癌（TSCC）是最常见的类型之一。尽管近年来治疗策略取得了进展，但 TSCC 的预后并未得到实质性改善。转移是 TSCC 患者死亡的主要原因之一；因此，有必要阐明TSCC转移的调控机制。本研究基于GEO数据集分析了TSCC中早期生长反应1（Egr-1）的表达，并使用Transwell实验测量了Egr-1对TSCC肿瘤细胞迁移和侵袭的影响。通过使用慢病毒感染在 Egr-1 敲低的细胞中过表达双特异性蛋白磷酸酶 1 (DUSP1)，确定了 DUSP1 在 Egr-1 调节的 TSCC 细胞迁移和侵袭中的作用。通过使用荧光素酶和 ChIP 检测，检测了 Egr-1 调节 DUSP1 的机制。在本研究中，证明Egr-1在TSCC中下调，并且Egr-1的敲除增加了TSCC细胞的迁移和侵袭。 Egr-1的表达也与DUSP1相关。 Egr-1敲低细胞中DUSP1的过度表达降低了细胞迁移和侵袭的水平。此外，还证明Egr-1的敲除抑制了DUSP1的启动子活性，并且鉴定了Egr-1调节DUSP1转录的位点。总之，本研究证明Egr-1通过调节DUSP1来调节TSCC细胞的迁移和侵袭，表明Egr-1和DUSP1作为TSCC治疗靶点的潜力。