Screening of candidate tumor-suppressor genes in 3p21.3 and investigation of the methylation of gene promoters in oral squamous cell carcinoma

Oncol Rep. 2013 Mar;29(3):1175-82. doi: 10.3892/or.2012.2213. Epub 2012 Dec 28.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck malignant tumor. however, its pathological mechanisms have not yet been elucidated. In the present study, we screened for candidate tumor-suppressor genes (TSGs) related to OSCC among 10 candidate genes located in 3p21.3, a region abundant with TSGs based on previous studies, using semi-quantitative reverse transcription PCR (RT-PCR). Three genes, GNAT1, SEMA3B and AXUD1, with low or no expression in OSCC tissues and the cell line TCA8113 were selected, and the promoter methylation status was further analyzed by methylation-specific PCR (MS-PCR). Hypermethylation in the promoter regions of SEMA3B was found in OSCC tissues, and a significant difference in the frequency of methylation of SEMA3B was observed between OSCC and non-cancerous tissues. Furthermore, TCA8113 cells treated with 5-Aza-Cdc started to re-express SEMA3B at a concentration of 5 µM or higher. Our study confirmed that three candidate TSGs with low expression may be involved in OSCC and that hypermethylation in promoter regions may contribute to the low expression of SEMA3B. These findings offer novel insights for clarifying the molecular mechanisms of tumorigenesis of OSCC as well as for aiding in its clinical diagnosis and therapeutic strategy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics*
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 3 / genetics*
  • DNA Methylation
  • Female
  • Genes, Tumor Suppressor
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Molecular Sequence Data
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Promoter Regions, Genetic
  • Semaphorins / genetics*
  • Semaphorins / metabolism
  • Sequence Analysis, DNA
  • Transcriptome
  • Transducin
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • CSRNP1 protein, human
  • GNAT1 protein, human
  • Membrane Glycoproteins
  • SEMA3B protein, human
  • Semaphorins
  • Heterotrimeric GTP-Binding Proteins
  • Transducin