title: Histone deacetylase inhibitors control the transcription and alternative splicing of prohibitin in thyroid tumor cells.
abstract: Prohibitin (PHB) is a ubiquitous protein with a number of different molecular functions. PHB is involved in tumorigenesis by exerting either a permissive or blocking action on tumor growth, depending on the cell context. In the present study, we investigated the effects of the histone deacetylase inhibitors (HDACis), trichostatin A (TSA) and sodium butyrate (NaB), on PHB expression in the thyroid tumor cell lines, TPC-1 and FRO. Both TSA and NaB increased PHB mRNA levels. Transfection experiments showed that the overexpression of HDAC1 or 2, but not 3, inhibited PHB promoter activity. The effects of TSA and NaB on the two major PHB mRNA splicing isoforms, were also investigated. Both TSA and NaB decreased the mRNA levels of the shorter isoform, but increased those of the longer isoform. Only the latter isoform contains a 3'UTR, which has been reported to exert a growth suppressive action. Thus, our data demonstrate that HDACis control both PHB transcription and alternative splicing. The effect of HDACis on PHB alternative splicing was not due to the modification of the expression of the ASF/SF2 splicing factor.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, and Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.forename: Nadia
authors.initials: N
authors.lastname: Passon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzoni
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008954:Models, Biological; D000091402:Prohibitins; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; C012589:trichostatin A