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微小RNA-802通过直接靶向丝裂原活化蛋白激酶激酶4在舌鳞状细胞癌中发挥肿瘤抑制作用。

MicroRNA-802 plays a tumour suppressive role in tongue squamous cell carcinoma through directly targeting MAP2K4.

作者信息

Wu Xiaozhen, Gong Zuode, Sun Lanying, Ma Long, Wang Qibao

机构信息

Department of Stomatology, Aerospace Center Hospital, Haidian District, Beijing, China.

Department of Endodontics, Jinan Stomatological Hospital, Jinan, Shandong, China.

出版信息

Cell Prolif. 2017 Jun;50(3). doi: 10.1111/cpr.12336. Epub 2017 Mar 20.

Abstract

OBJECTIVES

Tongue squamous cell carcinoma (TSCC) is the most common oral tumours. MicroRNAs play crucial roles in many cell processes including cell viability, development, apoptosis, migration and invasion. The role of miR-802 in the TSCC is still unknown.

MATERIALS AND METHODS

The miR-802 expression in TSCC tissues and cell lines was determined by quantitative real-time polymerase chain reaction. CCK-8 assay was performed to measure the cell viability, while the cell invasion assay was used to determine the cell invasion. Dual-luciferase reporter and western blot were used to confirm the potential target gene of miR-802.

RESULTS

In our study, we demonstrated that miR-802 expression was downregulated in TSCC tissues and cell lines. Elevated expression of miR-802 suppressed the TSCC cell viability and invasion. Moreover, enforced expression of miR-802 increased the expression of E-cadherin, while suppressed the expression of N-cadherin, Snail and Vimentin in the TSCC cell. In addition, we identified the mitogen-activated protein kinase 4 (MAP2K4) as a direct target gene of miR-802 in the TSCC cell. We also demonstrated that the expression of MAP2K4 was higher in the TSCC tissues than that in the adjacent normal tissues. Furthermore, the expression level of MAP2K4 was inversely associated with the expression of miR-802 in TSCC tissues. We also demonstrated that the MAP2K4 expression was upregulated in TSCC cell lines. Elevated expression of miR-802 inhibited TSCC cell viability and invasion through inhibiting MAP2K4 expression.

CONCLUSIONS

Our data revealed that miR-802 played as a tumour suppressor gene and might act as a therapeutic target in TSCC patients.

摘要

目的

舌鳞状细胞癌(TSCC)是最常见的口腔肿瘤。微小RNA在许多细胞过程中发挥关键作用,包括细胞活力、发育、凋亡、迁移和侵袭。miR-802在TSCC中的作用尚不清楚。

材料与方法

采用定量实时聚合酶链反应测定TSCC组织和细胞系中miR-802的表达。进行CCK-8测定以测量细胞活力,同时使用细胞侵袭测定来确定细胞侵袭。双荧光素酶报告基因和蛋白质印迹法用于确认miR-802的潜在靶基因。

结果

在我们的研究中,我们证明miR-802在TSCC组织和细胞系中表达下调。miR-802表达升高抑制了TSCC细胞的活力和侵袭。此外,miR-802的强制表达增加了E-钙黏蛋白的表达,同时抑制了TSCC细胞中N-钙黏蛋白、Snail和波形蛋白的表达。此外,我们确定丝裂原活化蛋白激酶4(MAP2K4)是TSCC细胞中miR-802的直接靶基因。我们还证明MAP2K4在TSCC组织中的表达高于相邻正常组织。此外,MAP2K4的表达水平与TSCC组织中miR-802的表达呈负相关。我们还证明MAP2K4在TSCC细胞系中表达上调。miR-802表达升高通过抑制MAP2K4表达抑制TSCC细胞活力和侵袭。

结论

我们的数据表明miR-802作为一种肿瘤抑制基因,可能成为TSCC患者的治疗靶点。

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