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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-14032018-113402
Document
Author
Full name
Nathália Cruz de Victo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Jacysyn, Jacqueline de Fátima (President)
Denapoli, Priscila Martins Andrade
Ferreira, Adilson Kleber
Franco, Marcelo de
Leite, Katia Ramos Moreira
Title in Portuguese
Importância de Dicer na progressão do melanoma e na resistência ao tratamento quimioterápico.
Keywords in Portuguese
Apoptose
Cisplatina
Dicer
Melanoma
Abstract in Portuguese
Dicer é um membro da família RNase III que controla a maturação de microRNA. A up-regulação de Dicer está associada a características agressivas e proliferação do melanoma. Nosso objetivo foi avaliar a expressão de Dicer em amostras de pacientes com melanoma nos diferentes estadios e em linhagens celulares de melanoma correlacionando a expressão de Dicer com progressão tumoral e resistência à apoptose. Comparamos Dicer no tecido de pacientes diagnosticados com melanoma em diferentes estadios, os resultados sugerem que o aumento da expressão de Dicer está associado à progressão do melanoma. Avaliamos nas linhagens knockdown para dicer1 a proliferação, capacidade clonogênica e sobrevida global. A linhagem celular SK-MEL-5 DICER KD foi mais suscetível à apoptose após o tratamento com cisplatina. Essa sensibilidade pode ser pela regulação dos receptores de morte, FAS e TNFR1, que estão envolvidos na indução de apoptose. Concluímos que o aumento na expressão de Dicer está relacionado com a progressão do Melanoma e com a resistência ao tratamento com cisplatina.
Title in English
The importance of Dicer in the progression of melanoma and resistance to chemotherapy treatment.
Keywords in English
Apoptosis
Cisplatin
Dicer
Melanoma
Abstract in English
Dicer is a member of the RNase III family that controls the maturation of microRNA. Up-regulation of Dicer is is only associated with melanoma. The aim of this study was to evaluate the expression of Dicer in samples of patients diagnosed with melanoma at different stages of the disease and in melanoma cell lines correlating the expression of Dicer with tumor progression and resistance to apoptosis. We compared Dicer protein in the tissue of patients diagnosed with melanoma at different stages. We observed that the increased dicer expression is associated with melanoma progression. Cell proliferation, clonogenic capacity and overall survival were evaluated in the knockdown cell lines for dicer1. The SK-MEL-5 DICER KD cell line was more susceptible to apoptosis after treatment with cisplatin. The regulation of FAS and TNFR1 death receptors expressed by knockdown cell line were important in the induction of apoptosis. We conclude that the increase in Dicer expression is related to the progression of Melanoma and resistance to treatment with cisplatin.
 
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Release Date
2020-03-13
Publishing Date
2018-03-14
 
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