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Doctoral Thesis
DOI
Document
Author
Full name
Fabianna Pansani
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Tirapelli, Daniela Pretti da Cunha (President)
Carvalho, Camila Albuquerque Melo de
Lizarte Neto, Fermino Sanches
Peria, Fernanda Maris
Title in Portuguese
Expressão dos microRNAs miR-126 e miR-873 e dos genes CASPASE-8 e C-FLIP em neuroesferas em linhagens de Glioblastoma U 343 submetidas ao tratamento com Radiação Ionizante e Temozolomida
Keywords in Portuguese
Apoptose
Gene
Glioblastoma
miRNA
Abstract in Portuguese
Introdução: O glioblastoma é considerado incurável, mesmo com a combinação de terapias (quimio e radioterapia), e ressecção cirúrgica, são necessárias novas abordagens terapêuticas para melhorar o prognóstico de pacientes com glioblastoma. Nas últimas décadas tem se desatacado na literatura pesquisas com foco em biologia molecular associada aos tumores cerebrais. Para o nosso estudo selecionamos o mecanismo de morte celular programada, a apoptose, assim dois microRNAs que atuam como possíveis regulados de genes pró e anti-apoptóticos. Objetivos: O objetivo do presente estudo foi avaliar a expressão dos genes CASPASE-8 e C-FLIP e dos microRNAs miR-126-5p e miR-873-5P em neuroesferas (NE) e células aderidas (CA) em linhagens celulares U343 submetidas ao tratamento com temozolomida (TMZ) e com radiação ionizante (RI) isolados e em associação (TMZ+RI). Material e métodos: A linhagem celular U343 foi submetida aos tratamentos com TMZ, RI e TMZ+RI. A verificação da expressão dos genes e miRNAs foi realizada utilizando o método de PCR em tempo real. Resultados e Conclusões: o gene CASPASE-8 apresentou aumento dos níveis de expressão nas CA no grupo tratado com RI quando comparadas aos demais grupos. O gene CFLIP apresentou aumento dos níveis de expressão nas CA e NE no grupo tratado com RI quando comparadas aos demais grupos. O miR-126 apresentou aumento nos níveis de expressão nas CA quando expostos a TMZ isolada quando comparadas aos demais grupos. O miR-873 apresentou aumento nos níveis de expressão nas CA nos grupos TMZ e TMZ+RI quando comparadas aos demais grupos
Title in English
Expression of the miR-126 and miR-873 microRNAs and of the CASPASE-8 and C-FLIP genes in neurospheres in U-343 Glioblastoma lines undergoing treatment with Ionizing Radiation and Temozolomide
Keywords in English
Apoptosis
Gene
Glioblastoma
miRNA
Abstract in English
Introduction: Introduction: Glioblastoma is considered incurable, even with the combination of therapies (chemo and radiotherapy), and surgical resection, new therapeutic approaches are needed to improve the prognosis of patients with glioblastoma. In recent decades, research has focused on molecular biology associated with brain tumors. For our study we selected the mechanism of programmed cell death, apoptosis, thus two microRNAs that act as possible regulated pro and anti-apoptotic genes. Objectives: This study aims to evaluate the expression of the following genes CASPASE-8 and C-FLIP and microRNAs miR-126- 5p and miR-873-5p in adhered cells (AC) and neurospheres (NS) from cell line U343 which were submitted to temozolomide (TMZ) and ionizing radiation (IR), isolated and associated (TMZ + IR). Methods: The cell line U343 were treated with TMZ, IR and TMZ+IR. The analysis of gene expression and miRNAs was performed using the PCR in real time. Results and Conclusions: The CASPASE-8 gene showed increased levels of expression in CA in the group treated with IR when compared to the other groups. The C-FLIP gene showed increased levels of expression in the CA and NE in the group treated with IR when compared to the other groups. The miR126 presented increased expression levels in CA when exposed to TMZ alone when compared to the other groups. The miR-873 presented increased expression levels in the CA in the TMZ and TMZ + RI groups when compared to the other groups
 
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FABIANNAPANSANI.pdf (5.15 Mbytes)
Publishing Date
2019-11-04
 
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