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错配修复基因 1 相关转录因子 1(OSR1)通过抑制 NF-κB 通路抑制舌鳞状细胞癌迁移和侵袭。

Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-κB pathway.

机构信息

Department of Head and Neck, Hospital of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China.

Department of Head and Neck, Hospital of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China.

出版信息

Eur J Pharmacol. 2018 Nov 15;839:33-39. doi: 10.1016/j.ejphar.2018.09.020. Epub 2018 Sep 19.

Abstract

Tongue squamous cell carcinoma (TSCC) is the most common cancers of oral, owing to the high invasive and metastatic ability, patients with TSCC have poor prognosis, it's important to explore the regulatory mechanism of TSCC invasion and metastasis. Previous studies suggest OSR1 suppresses the progression of gastric cancer and renal cell carcinoma, but its role in TSCC hasn't been studied. Here, we found OSR1 was downregulated in TSCC cells and specimens, Transwell and 3D spheroid invasion assay suggested OSR1 overexpression inhibited TSCC cell migration and invasion, while its knockdown promoted TSCC cell migration and invasion. Mechanism analysis found OSR1 expression was negatively correlated with NF-κB pathway and its targets. Western blot and NF-κB activity analysis suggested OSR1 inhibited NF-κB activity. Double inhibition of OSR1 and NF-κB significantly inhibited TSCC cell migration and invasion. These findings suggested OSR1 inhibited TSCC cell migration and invasion through inhibiting NF-κB pathway.

摘要

舌鳞状细胞癌(TSCC)是口腔最常见的癌症之一,由于其具有高侵袭性和转移性,TSCC 患者的预后较差,因此探索 TSCC 侵袭和转移的调控机制非常重要。先前的研究表明,OSR1 抑制胃癌和肾细胞癌的进展,但它在 TSCC 中的作用尚未被研究。在这里,我们发现 OSR1 在 TSCC 细胞和标本中下调,Transwell 和 3D 球体侵袭试验表明 OSR1 过表达抑制了 TSCC 细胞的迁移和侵袭,而其敲低则促进了 TSCC 细胞的迁移和侵袭。机制分析发现 OSR1 的表达与 NF-κB 途径及其靶标呈负相关。Western blot 和 NF-κB 活性分析表明 OSR1 抑制 NF-κB 活性。OSR1 和 NF-κB 的双重抑制显著抑制了 TSCC 细胞的迁移和侵袭。这些发现表明,OSR1 通过抑制 NF-κB 途径抑制了 TSCC 细胞的迁移和侵袭。

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