Credendino, Sara Carmela (2017) Characterization of a Novel Long Non-coding RNA Involved in Thyroid Differentiation. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Characterization of a Novel Long Non-coding RNA Involved in Thyroid Differentiation
Creators:
CreatorsEmail
Credendino, Sara Carmelasaracarmela.credendino@unina.it
Date: 6 April 2017
Number of Pages: 44
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Dottorato: Medicina molecolare e biotecnologie mediche
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricovittorioenrico.avvedimento@unina.it
Tutor:
nomeemail
De Vita, GabriellaUNSPECIFIED
Date: 6 April 2017
Number of Pages: 44
Uncontrolled Keywords: LncRNAs, thyroid, miRNAs
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/03 - Genetica medica
Date Deposited: 03 May 2017 08:45
Last Modified: 13 Mar 2018 11:24
URI: http://www.fedoa.unina.it/id/eprint/11541
DOI: 10.6093/UNINA/FEDOA/11541

Abstract

Thyroid is the endocrine gland that most frequently undergoes to congenital disorders or neoplastic transformation and despite its organogenesis is well characterized, molecular bases of early thyroid differentiation are still obscure. During last years, long non-coding RNAs (lncRNA) have acquired increasing relevance in many biological processes, such as differentiation and cancer. In E10.5 mouse thyroid bud the most enriched transcript resulted to be a poorly characterized lncRNA, that we named Thybe1 (thyroid bud enriched 1). Thybe1 is an antisense transcript of the protein-coding gene klhl14, also enriched in thyroid bud, to which it partially overlaps in a head-to-head arrangement. To shed light on its role, in this work we characterize such novel lncRNA, investigating its role in thyroid differentiation and its possible mechanism of action. Interestingly, our data reveal that Thybe1 is required for thyroid differentiation, in vitro, and is able to compete, for miR182a-5p binding, with Pax8 and Bcl2, both playing a key role in thyroid survival and differentiation. Moreover, we observed that Thybe1 is dramatically repressed during thyroid carcinogenesis, being inversely correlated with miR182a-5p expression, both in vitro and in vivo. Furthermore, we noted that Thybe1 expression positively correlates with that of Klhl14 in several cell types, suggesting that this lncRNA is also able to act in cis on this target. In conclusion we describe for the first time a lncRNA involved in thyroid differentiation and carcinogenesis, and start to highlight its ability to act as a competing endogenous RNA for key developmental genes, thus identifying a novel candidate gene playing a role in thyroid development defects and cancer.

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