MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma

作者：Chang Cheng Chi; Yang Yu Jen; Li Yue Ju; Chen Szu Ta; Lin Been Ren; Wu Tai Sheng; Lin Sze Kwen; Kuo Mark Yen Ping; Tan Ching Ting^*

来源：Oral Oncology, 2013, 49(9): 923-931.

DOI：10.1016/j.oraloncology.2013.03.430

• miRNA-17
• miRNA-20a
• Oral squamous cell carcinoma
• Migration
• ITG beta 8

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.

• 出版日期2013-9