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miR-940 通过调控 CXCR2/NF-κB 系统介导的上皮-间充质转化抑制舌鳞癌细胞的迁移和侵袭。

MiR-940 inhibits migration and invasion of tongue squamous cell carcinoma via regulatingCXCR2/NF-κB system-mediated epithelial-mesenchymal transition.

机构信息

Department of Oral and Maxillofacial Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2019 Nov;392(11):1359-1369. doi: 10.1007/s00210-019-01671-w. Epub 2019 Jun 18.

DOI:10.1007/s00210-019-01671-w
PMID:31214736
Abstract

Tongue squamous cell carcinoma (TSCC) is one of the most common incident oral cancers, which is accompanied by high rate of metastasis and recurrence. It has been demonstrated that elevated interleukin-8 (IL-8) promoted metastasis of various cancers via regulating epithelial-mesenchymal transition (EMT) process, whereas the accurate mechanism is left to be elucidated. The present work was aimed to investigate the role of microRNA-940 (miR-940)/C-X-C chemokine receptor type 2 (CXCR2) system in the metastasis ability and EMT process of IL-8-treated TSCC cells and further explore the underlying mechanisms. We found that miR-940 up-regulation inhibited IL-8-induced migration and invasion, which could be deprived by CXCR2 silence. We also observed that miR-940 suppressed epithelial marker E-cadherin expression while increased mesenchymal markers N-cadherin and Twist levels in IL-8-stimulated TSCC cells. Besides, IL-8-induced invasion and EMT process of TSCC cells were impeded in the present of the NF-κB inhibitor, PDTC or BAY117082. In conclusion, our data demonstrated that miR-940/CXCR2 system regulated the metastasis of TSCC cells via NF-κB-induced EMT process.

摘要

舌鳞状细胞癌(TSCC)是最常见的口腔癌之一,其转移和复发率较高。已经证明,白细胞介素-8(IL-8)通过调节上皮-间充质转化(EMT)过程促进了各种癌症的转移,但其确切机制尚待阐明。本研究旨在探讨微小 RNA-940(miR-940)/C-X-C 趋化因子受体 2(CXCR2)系统在 IL-8 处理的 TSCC 细胞转移能力和 EMT 过程中的作用,并进一步探讨其潜在机制。我们发现 miR-940 的上调抑制了 IL-8 诱导的迁移和侵袭,而沉默 CXCR2 则可以消除这种抑制作用。我们还观察到 miR-940 抑制了上皮标志物 E-钙黏蛋白的表达,同时增加了 IL-8 刺激的 TSCC 细胞中间充质标志物 N-钙黏蛋白和 Twist 的水平。此外,NF-κB 抑制剂 PDTC 或 BAY117082 可抑制 IL-8 诱导的 TSCC 细胞侵袭和 EMT 过程。总之,我们的数据表明,miR-940/CXCR2 系统通过 NF-κB 诱导的 EMT 过程调节 TSCC 细胞的转移。

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