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

被引:29
|
作者
House, Reniqua P. [1 ,2 ]
Talwar, Sudha [1 ,2 ]
Hazard, E. Starr [3 ]
Hill, Elizabeth G. [4 ]
Palanisamy, Viswanathan [1 ,2 ]
机构
[1] Med Univ S Carolina, Coll Dent Med, Dept Oral Hlth Sci, Charleston, SC 29425 USA
[2] Med Univ S Carolina, Coll Dent Med, Ctr Oral Hlth Res, Charleston, SC 29425 USA
[3] Med Univ S Carolina, Div Bioinformat, Charleston, SC 29425 USA
[4] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA
关键词
oral squamous cell carcinoma; CELF1; mRNA splicing and mRNA turnover; CANCER; CUGBP1; PROLIFERATION; CUG-BP1; CYTOSCAPE; PATHWAY; HEAD; MDA-7/IL-24; SEQUENCES; APOPTOSIS;
D O I
10.18632/oncotarget.6204
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:43620 / 43634
页数:15
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