RNA-binding protein CELF1 promotes tumor growth and alters gene expression in oral squamous cell carcinoma

Oncotarget. 2015 Dec 22;6(41):43620-34. doi: 10.18632/oncotarget.6204.

Abstract

The RNA binding protein CELF1 (also known as CUGBP1) is emerging as a critical regulator of cancer cell proliferation and apoptosis. Here, to provide a global prospective of CELF1 regulation of oral squamous cell carcinoma, we performed RNA-sequencing in oral cancer cells and CELF1 overexpression analysis in non-malignant human oral keratinocytes. Our approaches identified 1283 mRNAs differentially regulated as a function of CELF1 expression and more importantly CELF1 promoted alternative splicing of several target pre-mRNAs, which are known to be involved in various cancer biological processes. Overexpression of CELF1 in non-malignant human oral keratinocytes protected cells against oxidative damage and altered gene expression patterns. Finally, we provide evidence that reduction of CELF1 protein using a xenograft tumorigenesis mouse model decreased tumor growth. Altogether, these data provided a comprehensive view of the CELF1 mRNA regulatory network in oral cancer and suggests that CELF1 and/or its target mRNAs are viable candidates for therapeutic intervention.

Keywords: CELF1; mRNA splicing and mRNA turnover; oral squamous cell carcinoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • CELF1 Protein / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line
  • Gene Expression Regulation, Neoplastic / genetics*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Heterografts
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoprecipitation
  • Male
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck
  • Transcriptome
  • Transfection

Substances

  • CELF1 Protein