Original Paper

Journal of Cancer Research and Clinical Oncology

, Volume 135, Issue 5, pp 739-747

Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas

  • Feng GaoAffiliated withState Key Laboratory for Dental Medicines and West China College of Stomatology, Sichuan University
  • , Canhua HuangAffiliated withState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University
  • , Mei LinAffiliated withState Key Laboratory for Dental Medicines and West China College of Stomatology, Sichuan University
  • , Zhi WangAffiliated withState Key Laboratory for Dental Medicines and West China College of Stomatology, Sichuan University
  • , Jun ShenAffiliated withState Key Laboratory for Dental Medicines and West China College of Stomatology, Sichuan University
  • , Haiyuan ZhangAffiliated withOncology Research Institute, National University of Singapore
  • , Lu JiangAffiliated withState Key Laboratory for Dental Medicines and West China College of Stomatology, Sichuan University
  • , Qianming ChenAffiliated withState Key Laboratory for Dental Medicines and West China College of Stomatology, Sichuan University Email author 

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Abstract

Purpose

RUNX3 is a functionally important component in transforming growth factor-beta (TGF-β) mediated signaling pathway. Epigenetic silencing expression of RUNX3, as well as aberrant cytoplasmic retention of RUNX3 protein are causely involved in gastric carcinogenesis. Here, we examined the expression of RUNX3 gene and protein in oral squamous cell carcinomas (OSCCs) and analyzed the methylation status of RUNX3 promoter region.

Methods

About 10 normal oral mucosa and 30 OSCCs were collected to examine RUNX3 expression by RT-PCR analysis and immunohistochemistry assay using anti-RUNX3 monoclonal antibody R3-6E9. Methylation-specific PCR was carried out on the same specimens to analyze the methylation status of RUNX3 promoter. In addition, the stored paraffin-embedded specimens, including 40 oral leucoplakia (OLK) and 120 OSCCs, were examined by immunohistochemistry assay.

Results

RUNX3 gene and protein were underexpressed in OSCCs due to promoter hypermethylation. Protein mislocalization occured frequently. Both downregulation of RUNX3 protein expression (P = 0.001) and protein mislocalization (P = 0.001) were correlated with the differentiation grades in OSCCs.

Conclusions

RUNX3 plays an important role in oral carcinogenesis. It may be a useful diagnostic marker and a potential therapeutic target for OSCC.

Keywords

Hypermethylation Runt-related transcription factor 3 Oral squamous cell carcinoma Methylation-specific PCR Protein mislocalization