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)
Summary
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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