title: A TSH-CREB1-microRNA loop is required for thyroid cell growth.
abstract: MicroRNA (miRNA or miR) are an important class of regulators that participate in such biological functions as development, cell proliferation, differentiation, and apoptosis. The aim of this study was to elucidate the role of miRNA in cell proliferation using a unique cell system, namely thyroid cells that require thyrotropin for their growth. Here, we report the identification of a set of five specific miRNA (miR-1, miR-28-A, miR-290-5p, miR-296-3p, and miR-297a), whose down-regulation by thyrotropin is required for thyroid cell growth. In fact, overexpression of these miRNA negatively affects cell growth. We show that three of these miRNA target cAMP-responsive element binding protein (CREB)1, a thyrotropin-activated transcription factor, and that CREB1 binds the regulatory regions of the down-regulated miRNA. Hence, these data indicate that a synergistic loop involving thyrotropin, CREB1, and miRNA is required for thyroid cell proliferation.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Leone
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Angelo
authors.forename: Angelo
authors.initials: A
authors.lastname: Ferraro
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.forename: Ileana
authors.initials: I
authors.lastname: Rubio
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Croce
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology*; D013972:Thyrotropin / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D056742:Cyclin D2; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; D013972:Thyrotropin