title: PATZ1 is a target of miR-29b that is induced by Ha-Ras oncogene in rat thyroid cells.
abstract: The regulatory transcriptional factor PATZ1 is constantly downregulated in human thyroid cancer where it acts as a tumour suppressor by targeting p53-dependent genes involved in Epithelial-Mesenchymal Transition and cell migration. The aim of the present work was to elucidate the upstream signalling mechanisms regulating PATZ1 expression in thyroid cancer cells. The bioinformatics search for microRNAs able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-29b since it was found upregulated in rat thyroid differentiated cells transformed by the Ha-Ras oncogene towards a high proliferating and high migratory phenotype resembling that of anaplastic carcinomas. Functional assays confirmed PATZ1 as a target of miR-29b, and, consistently, an inverse correlation between miR-29b and PATZ1 protein levels was found upon induction of Ha-Ras oncogene expression in these cells. Interestingly, restoration of PATZ1 expression in rat thyroid cells stably expressing the Ha-Ras oncogene decreased cell proliferation and migration, indicating a key role of PATZ1 in Ras-driven thyroid transformation. Together, these results suggest a novel mechanism regulating PATZ1 expression based on the upregulation of miR-29b expression induced by Ras oncogene.
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Vitiello
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Valentino
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: De Menna
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Crescenzi
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Francesca
authors.affiliation: National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Rea
authors.affiliation: National Cancer Institute "Fondazione Giovanni Pascale", IRCCS, 80131 Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: De Vita
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cerchia
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D035683:MicroRNAs / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: C528429:Hras protein, rat; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D015513:Oncogene Proteins; C000625944:Patz1 protein, rat; D014157:Transcription Factors; D018631:ras Proteins