4.3 Article

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

Journal

ONCOTARGET
Volume 6, Issue 41, Pages 43620-43634

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6204

Keywords

oral squamous cell carcinoma; CELF1; mRNA splicing and mRNA turnover

Funding

  1. National Institute of General Medicine [P30 GM103331]

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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.

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