Abstract

BackgroundmiR-195 is aberrantly expressed in multiple types of disease. But little is known about the dysregulation of miR-195 in tongue squamous cell carcinoma (TSCC). In this study, we investigated the roles of miR-195 in the development and progression of TSCC.MethodsUsing quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we evaluated miR-195 expression in TSCC samples from 81 patients. Overall survival of these patients was examined using Kaplan–Meier curves with log-rank tests and the Cox proportional hazards model. The expression of two known miR-195 target genes, Cyclin D1 and Bcl-2, was also examined in the TSCC samples by immunohistochemistry. The effects of miR-195 overexpression on cell cycle progression and apoptosis and its effects on the expression of Cyclin D1 and Bcl-2 were examined in transfected TSCC cell lines (SCC-15 and Cal27) using fluorescence-activated cell sorting assays, luciferase reporter assays, and Western blots.ResultsReduced miR-195 expression was associated with tumor size and the clinical stage of TSCC tumors. Kaplan–Meier survival analysis indicated that the TSCC patients with reduced expression of miR-195 had poor overall survival and in multivariable analyses low levels of miR-195 emerged as an independent prognostic factor for this clinical outcome. Levels of miR-195 expression were inversely correlated with the expression of Cyclin D1 and Bcl-2. Overexpression of miR-195 inhibited cell cycle progression, promoted apoptosis, and reduced Cyclin D1 and Bcl-2 expression in two TSCC cell lines.ConclusionsmiR-195 may have potential applications as a prognostic factor for TSCC patients.

Highlights

  • Head and neck squamous cell carcinoma, including cancers of oral cavity, oropharynx, larynx, and hypopharynx, represents the sixth most frequent solid cancer around the world [1]

  • We found that the expression of miR-195 was statistically significantly decreased in primary tongue squamous cell carcinoma (TSCC) compared with matched normal tissues and was associated with progression and prognosis of TSCC patients

  • We evaluated the expression levels of miR-195 in 81 pairs of TSCC and the adjacent histologically normal tissues. miR-195 expression was decreased in 65 of 81 (80.2%) tumor samples compared with their nonmalignant counterparts (Fig. 1A)

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Summary

Introduction

Head and neck squamous cell carcinoma, including cancers of oral cavity, oropharynx, larynx, and hypopharynx, represents the sixth most frequent solid cancer around the world [1]. Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well-known for its high rate of proliferation and nodal metastasis [2]. MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs that inhibit gene expression through the 39untranslated regions (39-UTRs) of their target messenger RNAs [5]. Because of their widespread control of gene expression, miRNAs play crucial roles in numerous biological processes, including cell growth, apoptosis, metabolism, and transformation [6,7,8]. Little is known about the dysregulation of miR-195 in tongue squamous cell carcinoma (TSCC). We investigated the roles of miR-195 in the development and progression of TSCC

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