Cheng-Chi Chang1, Yu-Jen Yang2, Yue-Ju Li3, Szu-Ta Chen4, Been-Ren Lin5, Tai-Sheng Wu3, Sze-Kwen Lin6, Mark Yen-Ping Kuo6, Ching-Ting Tan7. 1. Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan. 2. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan. 3. Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan. 4. Department of Pediatrics, National Taiwan University Hospital Yun-Lin Branch, Yunlin County, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. 6. Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan. 7. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: tanct5222@ntu.edu.tw.
Abstract
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) β8 as a direct target of miR-17/20a, and knockdown of ITGβ8 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.
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) β8 as a direct target of miR-17/20a, and knockdown of ITGβ8 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.
Authors: Hye Shin Lee; Mujeeburahiman Cheerathodi; Sankar P Chaki; Steve B Reyes; Yanhua Zheng; Zhimin Lu; Helena Paidassi; Celine DerMardirossian; Adam Lacy-Hulbert; Gonzalo M Rivera; Joseph H McCarty Journal: Mol Cell Biol Date: 2015-02-09 Impact factor: 4.272
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