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

House, Reniqua P.; Talwar, Sudha; Hazard, E. Starr; Hill, Elizabeth G.; Palanisamy, Viswanathan

doi:10.18632/oncotarget.6204

Cited by 31 publications

(27 citation statements)

References 68 publications

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“…RBPs can influence the fate of tumour cells through processes including, but not limited to, apoptosis and cell cycle arrest . Cellular senescence induced for example by cyclin‐dependent kinase inhibitors (CDKi) presents an alternative approach to conventional chemotherapy.…”

Section: Identification Of Pro‐oncogenic Factors In 3q26‐29mentioning

confidence: 99%

3q26‐29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes

Davidson

Shanks

2017

The FEBS Journal

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Head and neck squamous cell carcinoma (HNSCC) is significantly underrepresented in worldwide cancer research, yet survival rates for the disease have remained static for over 50 years. Distant metastasis is often present at the time of diagnosis, and is the primary cause of death in cancer patients. In the absence of routine effective targeted therapies, the standard of care treatment remains chemoradiation in combination with (often disfiguring) surgery. A defining characteristic of HNSCC is the amplification of a region of chromosome 3 (3q26‐29), which is consistently associated with poorer patient outcome. This review provides an overview of the role the 3q26‐29 region plays in HNSCC, in terms of both known and as yet undiscovered processes, which may have potential clinical relevance.

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Section: Identification Of Pro‐oncogenic Factors In 3q26‐29mentioning

confidence: 99%

3q26‐29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes

Davidson

Shanks

2017

The FEBS Journal

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“…The association of CUGBP1 with its mRNA targets influences their alternative splicing, translation and turnover [17]. CUGBP1 is ubiquitously expressed and plays a critical role in various physiological and pathological cellular processes, including skeletal muscle differentiation and atrophy [18][19][20][21], cell proliferation [22], heart development and disease [23][24][25], and tumour growth [26]. Recently, several studies indicate that CUGBP1 may be involved in metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice

Zhai

Yang

et al. 2016

Diabetologia

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Aims/hypothesis CUG-binding protein 1 (CUGBP1) is a multifunctional RNA-binding protein that regulates RNA processing at several stages including translation, deadenylation and alternative splicing, as well as RNA stability. Recent studies indicate that CUGBP1 may play a role in metabolic disorders. Our objective was to examine its role in endocrine pancreas function through gain-and loss-of-function experiments and to further decipher the underlying molecular mechanisms. Methods A mouse model in which type 2 diabetes was induced by a high-fat diet (HFD; 60% energy from fat) and mice on a standard chow diet (10% energy from fat) were compared. Pancreas-specific CUGBP1 overexpression and knockdown mice were generated. Different lengths of the phosphodiesterase subtype 3B (PDE3B) 3′ untranslated region (UTR) were cloned for luciferase reporter analysis. Purified CUGBP1 protein was used for gel shift experiments.Results CUGBP1 is present in rodent islets and in beta cell lines; it is overexpressed in the islets of diabetic mice. Compared with control mice, the plasma insulin level after a glucose load was significantly lower and glucose clearance was greatly delayed in mice with pancreas-specific CUGBP1 overexpression; the opposite results were obtained upon pancreas-specific CUGBP1 knockdown. Glucose-and glucagon-like peptide1 (GLP-1)-stimulated insulin secretion was significantly attenuated in mouse islets upon CUGBP1 overexpression. This was associated with a strong decrease in intracellular cAMP levels, pointing to a potential role for cAMP PDEs. CUGBP1 overexpression had no effect on the mRNA levels of PDE1A, 1C, 2A, 3A, 4A, 4B, 4D, 7A and 8B subtypes, but resulted in increased PDE3B expression. CUGBP1 was found to directly bind to a specific ATTTGTT sequence residing in the 3′ UTR of PDE3B and stabilised PDE3B mRNA. In the presence of the PDE3 inhibitor cilostamide, glucose-and GLP-1-stimulated insulin secretion was no longer reduced by CUGBP1 overexpression. Similar to CUGBP1, PDE3B was overexpressed in the islets of diabetic mice. Conclusions/interpretation We conclude that CUGBP1 is a critical regulator of insulin secretion via activating PDE3B. Repressing this protein might provide a potential strategy for treating type 2 diabetes.

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“…In the cytoplasm Celf1 controls mRNA stability, and translation 3 . CELF1 has been implicated in diverse human diseases including mis-regulation in several cancers 4 5 6 7 , up-regulation in Myotonic Dystrophy type 1 (DM1) 8 9 10 11 , and more recently it has been associated with Alzheimer disease 12 13 .…”

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confidence: 99%

Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1

Giudice

Xia

et al. 2016

Sci Rep

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The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development. RNA-sequencing of mRNA from homozygous neonatal hearts identified a network of cell cycle genes significantly up-regulated and down-regulation of ion transport and circadian genes. Cell cycle genes are enriched for Celf1 binding sites supporting a regulatory role in mRNA stability of these transcripts. We also identified a cardiac splicing network coordinated by Celf1 depletion. Target events contain multiple Celf1 binding sites and enrichment in GU-rich motifs. Identification of direct Celf1 targets will advance our knowledge in the mechanisms behind developmental networks regulated by Celf1 and diseases where Celf1 is mis-regulated.

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

Cited by 31 publications

References 68 publications

3q26‐29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes

3q26‐29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes

RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice

Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1

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