SUZ12 is a novel putative oncogene promoting tumorigenesis in head and neck squamous cell carcinoma

J Cell Mol Med. 2018 Jul;22(7):3582-3594. doi: 10.1111/jcmm.13638. Epub 2018 Apr 18.

Abstract

The suppressor of zest 12 (SUZ12), one of the core polycomb repressive complex 2 (PRC2) components, has increasingly appreciated as a key mediator during human tumorigenesis. However, its expression pattern and oncogenic roles in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored yet. Here, we sought to determine its expression pattern, clinicopathological significance and biological roles in HNSCC. Through data mining and interrogation from multiple publicly available databases, our bioinformatics analyses revealed that SUZ12 mRNA was significantly overexpressed in multiple HNSCC patient cohorts. Moreover, SUZ12 protein was markedly up-regulated in primary HNSCC samples from our patient cohort as assessed by immunohistochemical staining and its overexpression significantly associated with cervical node metastasis and reduced overall and disease-free survival. In the 4-nitroquinoline 1-oxide (4NQO)-induced HNSCC mouse model, increased SUZ12 immunostaining was observed along with disease progression from epithelial hyperplasia to squamous cell carcinoma in tongue. Furthermore, shRNA-mediated SUZ12 knock-down significantly inhibited cell proliferation, migration and invasion in HNSCC cells, and resulted in compromised tumour growth in vivo. Collectively, our data reveal that SUZ12 might serve as a putative oncogene by promoting cell proliferation, migration and invasion, and also a novel biomarker with diagnostic and prognostic significance for HNSCC.

Keywords: SUZ12; biomarker; head and neck squamous cell carcinoma; polycomb repressive complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Mice, Nude
  • Middle Aged
  • Neoplasm Proteins
  • Oncogenes
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Transcription Factors
  • Xenograft Model Antitumor Assays

Substances

  • Neoplasm Proteins
  • SUZ12 protein, human
  • Transcription Factors
  • Polycomb Repressive Complex 2