title: Identification of tumorigenesis-related mRNAs associated with RNA-binding protein HuR in thyroid cancer cells.
abstract: RNA binding proteins (RBPs) play a central role in cell physiology and pathology. Among them, HuR is a nuclear RBP, which shuttles to the cytoplasm to allow its RNA targets processing. HuR over-expression and delocalization are often associated to cell transformation. Numerous cancers display increased HuR protein levels and its high cytoplasmic levels has been associated with a worse prognosis.In our study, we first evaluated HuR expression in normal and cancer thyroid tissues and then evaluated its function in thyroid cell lines. HuR is over-expressed in all thyroid tumor tissues; high cytoplasmic levels are detected in all thyroid carcinomas. HuR silencing decreased cell viability and determined apoptotic cell death, in a non-tumorigenic (Nthy-ori-3.1) and a tumorigenic (BCPAP) thyroid cell line. Global transcriptome analysis indicated that HuR silencing, though having similar biological effects, induces distinct gene expression modifications in the two cell lines. By using the RIP-seq approach, the HuR-bound RNA profiles of different thyroid cell lines were evaluated. We show that in distinct cell lines HuR-bound RNA profiles are different. A set of 114 HuR-bound RNAs distinguishing tumorigenic cell lines from the non-tumorigenic one was identified.Altogether, our data indicate that HuR plays a role in thyroid tumorigenesis. Moreover, our findings are a proof of concept that RBP targets differ between cells with the same origin but with distinct biological behavior.
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Baldan
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Mio
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Allegri
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Ketty
authors.initials: K
authors.lastname: Conzatti
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Toffoletto
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.affiliation: IGA Technology Services Srl, 33100 Udine, Italy.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Radovic
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vascotto
authors.affiliation: Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.|Institute of Anatomic Pathology, University Hospital "S. Maria della Misericordia", 33100 Udine, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Di Loreto
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.|Institute of Medical Genetics, University Hospital "S. Maria della Misericordia", 33100 Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics*; D015996:Survival Rate; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: HuR; RIP-seq; RNA-binding proteins; RNA-seq