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Oral Oncol. 2013 Sep;49(9):923-931. doi: 10.1016/j.oraloncology.2013.03.430. Epub 2013 Apr 17.

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

Author information

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.

KEYWORDS:

3′ untranslated region; 3′UTR; CT; IPA; ITGβ8; LAMA3; Migration; OSCC; Oral squamous cell carcinoma; ROC; comparative threshold; ingenuity pathway analysis; integrin β8; laminin α3; miRNA; miRNA-17; miRNA-20a; microRNA; oral squamous cell carcinoma; receiver-operating characteristics

[Indexed for MEDLINE]

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