title: Overexpression of RNA-binding protein CELF1 prevents apoptosis and destabilizes pro-apoptotic mRNAs in oral cancer cells.
abstract: CELF1 RNA-binding protein, otherwise called CUGBP1, associates and coordinates the degradation of GU-rich element (GRE) containing mRNA's encoding factors important for cell growth, migration and apoptosis. Although many substrates of CELF1 have been identified, the biological significance of CELF1-mediated mRNA decay remains unclear. As the processes modulated by CELF1 are frequently disrupted in cancer, we investigated the expression and role of CELF1 in oral squamous cancer cells (OSCCs). We determined that CELF1 is reproducibly overexpressed in OSCC tissues and cell lines. Moreover, depletion of CELF1 reduced proliferation and increased apoptosis in OSCCs, but had negligible effect in non-transformed cells. We found that CELF1 associates directly with the 3'UTR of mRNAs encoding the pro-apoptotic factors BAD, BAX and JunD and mediates their rapid decay. Specifically, 3'UTR fragment analysis of JunD revealed that the GRE region is critical for binding with CELF1 and expression of JunD in oral cancer cells. In addition, silencing of CELF1 rendered BAD, BAX and JunD mRNAs stable and increased their protein expression in oral cancer cells. Taken together, these results support a critical role for CELF1 in modulating apoptosis and implicate this RNA-binding protein as a cancer marker and potential therapeutic target.
authors: Department of Craniofacial Biology and Center for Oral Health Research, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors: Sudha
authors: S
authors: Talwar
authors: Sundaravadivel
authors: S
authors: Balasubramanian
authors: Santhanalakshmi
authors: S
authors: Sundaramurthy
authors: Reniqua
authors: R
authors: House
authors: Carol J
authors: CJ
authors: Wilusz
authors: Dhandapani
authors: D
authors: Kuppuswamy
authors: Nisha
authors: N
authors: D'Silva
authors: Marion Boyd
authors: MB
authors: Gillespie
authors: Elizabeth Goodwin
authors: EG
authors: Hill
authors: Viswanathan
authors: V
authors: Palanisamy
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D000067879:CELF1 Protein; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C494819:BAD protein, human; C494826:BAX protein, human; D014408:Biomarkers, Tumor; D000067879:CELF1 Protein; C102843:CELF1 protein, human; C559371:JunD protein, human; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein
keywords: CELF1; caspase; mRNA stability; oral cancer; pro-apoptosis; translation