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Master's Dissertation
DOI
https://doi.org/10.11606/D.87.2016.tde-23082016-104319
Document
Author
Full name
Jean Lucas Parpinelli Barbosa
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Severino, Patrícia (President)
Lotfi, Claudimara Ferini Pacicco
Strauss, Bryan Eric
Title in Portuguese
Mecanismos de ação do miRNA-196a sobre a progressão do ciclo celular em câncer.
Keywords in Portuguese
Carcinoma epidermoide de cabeça e pescoço
Ciclo celular
MicroRNA
Abstract in Portuguese
Os microRNAs regulam uma parte significativa dos genes humanos, dentre os quais genes responsáveis por controlar o ciclo celular. Em estudos anteriores identificou-se maior expressão do miR-196a em amostras de carcinoma epidermoide de cabeça e pescoço (CECP), um dos tipos de tumor mais comuns no mundo, quando comparadas a margens cirúrgicas. Através de estudos de ganho de função, observou-se diminuição da proliferação de queratinócitos orais e de linhagens celulares após a super-expressão do miR-196a. Neste trabalho avaliamos a expressão gênica e de proteínas em linhagem celular em diferentes tempos após super-expressão do microRNA. Identificamos alterações na expressão de genes ativadores e repressores do ciclo e diminuição na expressão de p27, alvo do miR-196a. Observamos que após 48 horas de super-expressão a maioria dos genes repressores do ciclo celular estavam mais expressos, fato possivelmente associado à diminuição da proliferação. Sugerimos que a super-expressão de miR-196a possa ser considerada como uma possível terapia para o tratamento do câncer.
Title in English
Mechanisms of action of microRNA-196 on cell cycle progression in cancer.
Keywords in English
Cell cycle
Head and neck squamous cells carcinoma
MicroRNA
Abstract in English
MicroRNAs regulate a proportion of human genes, among which genes responsible for cell cycle control. Squamous cell carcinoma of head and neck (HNSCC) is among the most common malignancies worldwide. In a previous study we identified enhanced expression of miR-196a in HNSCC samples compared with surgical margins and increased expression of miR-196a in HNSCC-derived cell lines compared to oral keratinocytes. Following a gain of function study, there was decreased oral keratinocyte and HNSCC cell line proliferation. In this study, gene expression and protein levels were assessed within 48 hours after overexpression of miR-196a. Changes in gene expression levels of cell cycle activators and repressors was observed, as well as the decreased expression of p27, a gene targeted by miR-196a. At 48 hours following the overexpression of miR-196a most inhibitor genes were more expressed. This fact could be associated with the decrease in cell proliferation after overexpression of miR-196a. We suggest that the overexpression of miR-196a is considered a tool for CECP therapy.
 
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Release Date
2020-08-23
Publishing Date
2016-08-23
 
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