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Abstract：
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.
摘要：
口腔鳞状细胞癌（OSCC）是头颈部最常见的恶性肿瘤之一，在OSCC中，舌鳞状细胞癌（TSCC）是最常见的类型之一。尽管治疗策略最近取得了进展，TSCC的预后没有显著改善.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。在本研究中,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测定法测量了Egr-1在TSCC肿瘤细胞迁移和侵袭中的作用。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TSCC细胞迁移和侵袭中的作用。通过使用荧光素酶和ChIP测定，检测到DUSP1受Egr-1调控的机制。在本研究中,结果表明，Egr-1在TSCC中下调，Egr-1的敲除增加了TSCC细胞的迁移和侵袭能力。Egr-1的表达也与DUSP1相关。DUSP1在Egr-1敲低细胞中的过表达,降低细胞迁移和侵袭水平。此外，已证明Egr-1的敲低抑制了DUSP1的启动子活性，并鉴定了Egr-1调节DUSP1转录的位点。总之,本研究表明Egr-1通过调节DUSP1调节TSCC细胞的迁移和侵袭，提示Egr-1和DUSP1作为TSCC治疗靶点的潜力。
