MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma
MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2013.03.430
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发表时间：
2013-09-01
期刊：
影响因子：
4.8
通讯作者：
Tan, Ching-Ting
中科院分区：
文献类型：
--
作者：
Chang, Cheng-Chi;Yang, Yu-Jen;Tan, Ching-Ting
目的：口腔鳞状细胞癌（Oral squamous cell carcinoma，OSCC）占口腔癌的90%以上，是世界范围内癌症死亡的主要原因。早期诊断可能会增加这种肿瘤的生存率。微小RNA干扰肿瘤的进展至关重要，但其在口腔鳞癌中的迁移机制尚不清楚。为了探讨miRNA是否是可能的预后标志物和潜在的机制，我们从TW 2.6细胞中培养了一个高度迁移的TW 2.6 MS-10细胞来研究这个问题。实时荧光定量RT-PCR检测目的miRNA与口腔鳞癌患者的病理状态相关。结果：与TW2.6细胞相比，MS-10细胞中的miR-17-92（包括miR-17、miR-19 b、miR-20 a和miR-92 a）表达显著下调。该簇的过表达降低了OSCC细胞系的迁移能力。我们进一步证实了miR-17和miR-20 a是miR-17-92簇中调节OSCC迁移的主要miRNA。临床上，miR-17/20 a与TNM分期、淋巴结转移呈负相关。结论：miR-17/20 a可作为OSCC患者预后的预测因子和肿瘤迁移抑制剂。(c)2013爱思唯尔有限公司保留所有权利。
Objectives: Oral squamous cell carcinoma (OSCC) accounts for >90% oral cancer which is a leading cause of cancer death worldwide. Early diagnosis may well offer an opportunity to increase survival to this neoplasm. Micro(mi)RNA-interfered cancer progression is crucial, yet its migration machinery of OSCC is still unknown. To access whether the possible miRNA prognostic markers and underlying mechanisms, we developed a highly migratory TW2.6 MS-10 cells from TW2.6 cells to investigate the issue.Materials and methods: miRNA profiling was performed on TW2.6 and TW2.6 MS-10. Target miRNA was correlated to pathological status in OSCC patients by real-time RT-PCR. A downstream effector was identified using a bioinformatics analysis, and a 3'-untranslated region (UTR) reporter assay was used.Results: An miRNA cluster, miR-17-92, including miR-17, miR-19b, miR-20a, and miR-92a, was found to be significantly down-regulated in TW2.6 MS-10 compared to TW2.6 cells. Overexpression of this cluster decreased the migratory ability of OSCC cell lines. We further demonstrated that miR-17 and miR-20a are the main miRNAs of miR-17-92 cluster which modulate OSCC migration. Clinically, miR-17/20a showed negative correlation with TNM stage and lymphatic metastasis. Through a bioinformatics screening analysis and 3'UTR reporter assay, we confirmed the integrin (ITG) beta 8 as a direct target of miR-17/20a, and knockdown of ITG beta 8 reduced cell migratory capability of OSCC.Conclusions: miR-17/20a acts as a prognostic predictor of OSCC patients' outcome and a tumor migration suppressor miRNA. (c) 2013 Elsevier Ltd. All rights reserved.