Oncogenic features of PHF8 histone demethylase in esophageal squamous cell carcinoma

PLoS One. 2013 Oct 11;8(10):e77353. doi: 10.1371/journal.pone.0077353. eCollection 2013.

Abstract

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. It has been reported that histone demethylases are involved in the carcinogenesis of certain types of tumors. Here, we studied the role of one of the histone lysine demethylases, plant homeodomain finger protein 8 (PHF8), in the carcinogenesis of esophageal squamous cell carcinoma (ESCC). Using short hairpin RNA via lentiviral infection, we established stable ESCC cell lines with constitutive downregulation of PHF8 expression. Knockdown of PHF8 in ESCC cells resulted in inhibition of cell proliferation and an increase of apoptosis. Moreover, there were reductions of both anchorage-dependent and -independent colony formation. In vitro migration and invasion assays showed that knockdown of PHF8 led to a reduction in the number of migratory and invasive cells. Furthermore, downregulation of PHF8 attenuated the tumorigenicity of ESCC cells in vivo. Taken together, our study revealed the oncogenic features of PHF8 in ESCC, suggesting that PHF8 may be a potential diagnostic marker and therapeutic target for ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Disease Models, Animal
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Histone Demethylases / genetics*
  • Histone Demethylases / metabolism
  • Humans
  • Mice
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tumor Burden / genetics
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

Substances

  • Oncogene Proteins
  • Transcription Factors
  • Histone Demethylases
  • PHF8 protein, human

Grants and funding

This work was supported in part by the Albert and Margaret Alkek Foundation of Department of Medicine of Baylor College of Medicine, the National Natural Science Foundation of China (81272447), and the National Key Basic Research Program of China (2012CB526600). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.