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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
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RUNX3 has an oncogenic role in head and neck cancer

Takaaki Tsunematsu1, Yasusei Kudo, Shinji Iizuka

  • 1Division of Frontier Medical Science, Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

Plos One
|June 13, 2009
PubMed
Abstract

Insights

Runt-related transcription factor 3 (RUNX3) surprisingly acts as an oncogene in head and neck squamous cell carcinoma (HNSCC), promoting cancer growth and resistance to apoptosis. RUNX3 may serve as a marker for HNSCC malignancy and drug response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Runt-related transcription factor 3 (RUNX3) is typically a tumor suppressor.
  • RUNX3 is involved in the transforming growth factor-beta (TGF-β) tumor suppression pathway.
  • Preliminary data indicated higher RUNX3 expression in head and neck squamous cell carcinoma (HNSCC) than normal tissues.

Purpose of the Study:

  • To investigate the role of RUNX3 in HNSCC.
  • To determine if RUNX3 has an oncogenic function in HNSCC.

Main Methods:

  • Analysis of RUNX3 expression in HNSCC tissues.
  • Experimental manipulation of RUNX3 levels (overexpression and knockdown) in HNSCC cells.
  • Assessment of cell growth, apoptosis, and tumorsphere formation.
  • Correlation analysis with methylation status.

Main Results:

  • RUNX3 was frequently expressed in HNSCC and correlated with malignant behavior.
  • RUNX3 overexpression promoted HNSCC cell growth and inhibited apoptosis.
  • RUNX3 knockdown reversed these effects.
  • RUNX3 overexpression enhanced tumorsphere formation.
  • RUNX3 expression correlated with promoter methylation status; low RUNX3 in normal cells was linked to promoter methylation.

Conclusions:

  • RUNX3 exhibits an oncogenic role in HNSCC.
  • Demethylation may contribute to RUNX3 upregulation in HNSCC.
  • RUNX3 expression can predict HNSCC malignancy and response to chemotherapy.

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