Vincenza Leone1, Daniela D'Angelo, Pierlorenzo Pallante, Carlo Maria Croce, Alfredo Fusco. 1. Istituto di Endocrinologia ed Oncologia Sperimentale del CNR (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 80131 Naples, Italy.
Abstract
CONTEXT: MicroRNA (miRNA or miR) have emerged as an important class of short endogenous RNA that act as post-transcriptional regulators of gene expression and have a critical role in cell proliferation and differentiation. OBJECTIVES: The aim of this study was to elucidate the role of miRNA in the proliferation of differentiated thyroid cells that require TSH for their growth. DESIGN: To elucidate the role of miRNA in thyroid cell proliferation, we have analyzed the miRNA expression profile of PC Cl 3 cells before and after the stimulation by TSH. RESULTS: We report the identification of two specific miRNA (miR-23b and miR-29b) whose up-regulation by TSH is required for thyroid cell growth. We identified mothers against decapentaplegic homolog 3 (Smad3), a member of the TGF-β pathway that has an inhibitor role in thyroid follicular cell proliferation as a target of miR-23b and miR-29b. Functional studies demonstrated that the overexpression of miR-23b and miR-29b promotes thyroid cell growth. Interestingly, an increased expression of both these miRNA was also detected in experimental and human goiters. CONCLUSIONS: These findings support the idea that the regulation of miRNA expression synergizes with the traditional proliferation pathways in promoting cell growth.
CONTEXT: MicroRNA (miRNA or miR) have emerged as an important class of short endogenous RNA that act as post-transcriptional regulators of gene expression and have a critical role in cell proliferation and differentiation. OBJECTIVES: The aim of this study was to elucidate the role of miRNA in the proliferation of differentiated thyroid cells that require TSH for their growth. DESIGN: To elucidate the role of miRNA in thyroid cell proliferation, we have analyzed the miRNA expression profile of PC Cl 3 cells before and after the stimulation by TSH. RESULTS: We report the identification of two specific miRNA (miR-23b and miR-29b) whose up-regulation by TSH is required for thyroid cell growth. We identified mothers against decapentaplegic homolog 3 (Smad3), a member of the TGF-β pathway that has an inhibitor role in thyroid follicular cell proliferation as a target of miR-23b and miR-29b. Functional studies demonstrated that the overexpression of miR-23b and miR-29b promotes thyroid cell growth. Interestingly, an increased expression of both these miRNA was also detected in experimental and humangoiters. CONCLUSIONS: These findings support the idea that the regulation of miRNA expression synergizes with the traditional proliferation pathways in promoting cell growth.
Authors: Sébastien L Floor; Aline Hebrant; Jaime M Pita; Manuel Saiselet; Christophe Trésallet; Frederick Libert; Guy Andry; Jacques E Dumont; Wilma C van Staveren; Carine Maenhaut Journal: PLoS One Date: 2014-11-06 Impact factor: 3.240