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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2013.tde-24052014-091609
Document
Author
Full name
Luciana Machado Dzik
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Kimura, Edna Teruko (President)
Cella, Nathalie
Pasini, Fátima Solange
Title in Portuguese
A influência do microRNA miR-21 no câncer de tiróide.
Keywords in Portuguese
Células cultivadas de tumor
Neoplasias da tireóide
Nucleotídeos
Proliferação celular
RNA
Abstract in Portuguese
O carcinoma tiroidiano apresenta alterações na via MAPK, destacando-se o rearranjo RET/PTC. Alterações na expressão de microRNAs também são observadas. O aumento da expressão de miR-21 nos levou a analisar o papel deste na tumorigênese tiroidiana, bem como a influência da ativação oncogênica de RET/PTC3 durante este processo. A expressão de miR-21 foi analisada em 4 linhagens e a sua modulação foi realizada em células PCCL3 e KTC-2. RET/PTC3 foi ativado em células PTC3-5 e analisou-se a sua influência na expressão de miR-21 e na proliferação celular. Todas as linhagens expressam miR-21. A transfecção de anti-miR-21 em células KTC-2 inibiu em 80% a expressão deste miRNA, observando-se um aumento de SMAD7. A super-expressão de miR-21 em PCCL3 não alterou a proliferação. A indução de RET/PTC3 aumentou a expressão de miR-21 e diminui a proliferação, e quando ativado concomitante ao tratamento com TGFb-1, a diminuição na proliferação se acentuou, sugerindo que RET/PTC3 ative a via TGFb através da inibição de SMAD7 mediada por miR-21.
Title in English
The role of microRNA miR-21 thyroid cancer.
Keywords in English
Cell proliferation
Cultured tumor cells
Nucleotides
RNA
Thyroid neoplasms
Abstract in English
Alterations in MAPK signaling are common in thyroid cancer, including RET/PTC rearrangement. Additionally, several studies described the altered expression of microRNAs. The up-regulation of miR-21 on thyroid cancer led us to evaluate the role of this molecule on thyroid tumorigenesis, and also the influence of RET/PTC3 activation in this process. MiR-21 expression was analyzed in four thyroid cell lines, and the modulation of this miRNA was performed in KTC-2 and PCCL3 cells. PTC3-5 cells were used to analyze the influence of RET/PTC3 on miR-21 expression and cell proliferation. miR-21 expression was found in both cell lines. Anti-miR-21 transfection in KTC-2 cells decreased miR-21 levels in 80% and also increased SMAD7 expression. The up-regularion of RET/PTC3 increased miR-21 expression and decreased cell growth. The activation of RET/PTC3 combined to TGFb-1 treatment accentuated decrease in proliferation, suggesting that RET/PTC3 positively regulates TGFb pathway through miR-21-dependent SMAD7 inhibition.
 
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Release Date
2020-05-23
Publishing Date
2014-05-24
 
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