Prognostic implications of micoRNA miR-195 expression in human tongue squamous cell carcinoma

PLoS One. 2013;8(2):e56634. doi: 10.1371/journal.pone.0056634. Epub 2013 Feb 22.

Abstract

Background: miR-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.

Methods: Using 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.

Results: Reduced 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.

Conclusions: miR-195 may have potential applications as a prognostic factor for TSCC patients.

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Proliferation
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • In Vitro Techniques
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA-Directed DNA Polymerase
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / metabolism*
  • Tongue Neoplasms / pathology*

Substances

  • MIRN195 microRNA, human
  • MicroRNAs
  • RNA-Directed DNA Polymerase

Grants and funding

The authors have no support or funding to report.