Esposito, Matteo (2022) Investigating the role of Klhl14 in thyroid differentiation. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Investigating the role of Klhl14 in thyroid differentiation
Creators:
CreatorsEmail
Esposito, Matteomatteo.esposito@unina.it
Date: 10 March 2022
Number of Pages: 53
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Dottorato: Medicina molecolare e biotecnologie mediche
Ciclo di dottorato: 34
Coordinatore del Corso di dottorato:
nomeemail
Santoro, Massimomassimo.santoro@unina.it
Tutor:
nomeemail
De Vita, GabriellaUNSPECIFIED
Date: 10 March 2022
Number of Pages: 53
Keywords: differentiation, thyroid, klhl14, lncRNA, endoplasmic reticulum
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 05 - Scienze biologiche > BIO/18 - Genetica
Date Deposited: 17 Mar 2022 15:06
Last Modified: 28 Feb 2024 10:47
URI: http://www.fedoa.unina.it/id/eprint/14439

Collection description

Early molecular events of thyroid differentiation are not fully understood even though its organogenesis is well characterized. Over the last few decades, the recently described Kelch-like protein family caught the attention for its members ability to modulate differentiation processes and tumorigenesis by targeting specific protein for degradation. Klhl14, a member of this family, came out as one of the most enriched gene in E10.5 mouse thyroid bud, alongside with a previously uncharacterized lncRNA and Klhl14 natural antisense that was named by our group Thybe1/Klhl14-AS (as for thyroid bud enriched 1). Klhl14-AS has been recently described as a regulator of thyroid transcription factors and a modulator of Klhl14 expression, although little is known in Klhl14 involvement in thyroid differentiation. To understand Klhl14 role, in this work we characterized its capacity to modulate thyroid factors abundance in thyroid normal cells and to elicit a negative response in survivability and proliferation of thyroid transformed cells. We found that Klhl14 silencing does not only negatively affect thyroid specific protein abundance, but also increase the presence of Klhl14-AS, thyroid transcription factors FoxE1 and Pax8, and Bcl2, all described to regulate thyroid homeostasis. Moreover, Klhl14 alteration could also direct Nis and Thyroglobulin maturation and distribution in and out of the cell. Interestingly, we also observed a negative effect on thyroid transformed cells survival that is in line with a proposed tumor suppressor role of Klhl14 described in literature. In conclusion, we have described how the effects of tuning up or down Klhl14 expression in thyroid can induce a response that is likely to influence differentiation and homeostasis of this endocrine gland.

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