RNA-binding protein CELF1 promotes tumor growth and alters gene expression in oral squamous cell carcinoma.
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.
Department of Oral Health Sciences and Center for Oral Health Research, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
Reniqua P
RP
House
Department of Oral Health Sciences and Center for Oral Health Research, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
Sudha
S
Talwar
Division of Bioinformatics, Medical University of South Carolina, Charleston, SC, USA.
E Starr
ES
Hazard
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
Elizabeth G
EG
Hill
Department of Oral Health Sciences and Center for Oral Health Research, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
Viswanathan
V
Palanisamy
D000818:Animals; D015153:Blotting, Western; D000067879:CELF1 Protein / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome; D014162:Transfection
D000067879:CELF1 Protein
CELF1; mRNA splicing and mRNA turnover; oral squamous cell carcinoma