• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2020.tde-01062020-080224
Document
Author
Full name
Vinicius Marques Carneiro
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Carlotti Junior, Carlos Gilberto (President)
Duarte, Sinésio Grace
Tirapelli, Daniela Pretti da Cunha
Tone, Luiz Gonzaga
Title in Portuguese
Expressão dos microRNAs miR-27a, miR-216a e gene HNRNPU em meningiomas e suas correlações com a progressão tumoral
Keywords in Portuguese
Meningiomas
microRNAs
Perfil de expressão
Progressão tumoral
Abstract in Portuguese
Introdução: Os meningiomas são neoplasias intracranianas de crescimento lento e que se originam das células meningoteliais da aracnóide, representam mais de 33% dos tumores primários do sistema nervoso central. Constituem um grande desafio no seu manejo. O tratamento mais eficaz e preconizado é a máxima ressecção cirúrgica, sem comprometer a função neurológica do paciente. Uma neoplasia extremamente freqüente, escassas opções de tratamento adjuvante e pouco compreendida em âmbito molecular culmina em um ambiente desafiador e de suma importância médica para que novas terapias surjam e possam propiciar o melhor tratamento para os pacientes. Neste contexto tem se destacado o papel dos microRNAs, que são RNAs não-codificantes (ncRNAs) constituídos por 19 a 25 nucleotídeos, cuja função é o silenciamento do RNAm em nível pós-transcricional. Portanto, o objetivo do nosso estudo foi avaliar a expressão tecidual e plasmática dos miR-27a, miR-216a e gene HNRNPU. Pacientes e métodos: Os miRNAs miR- 27a, miR-216a e gene HNRNPU foram selecionados a partir de estudo prévio do nosso grupo pela técnica de análise em larga escala de microarrays, onde foram comparados meningiomas grau I com amostras controles de aracnóides. Neste trabalho foi avaliada a expressão destes miRNAs (tecido tumoral e plasma) e do gene HNRNPU, por meio da técnica de PCR em tempo real, em meningiomas grau I, II e III, respectivamente com 14, 14 e 6 pacientes. Resultados: A idade média foi de 55 anos, sendo 76,5%(26) dos casos mullheres e 23,5% (8) homens. Houve um aumento progressivo da proporção do sexo masculino à medida que o grau tumoral se eleva (grau 1 - 7,1%, grau 2 - 28,6% e grau 3 - 50%). A proporção de meningiomas de convexidade acompanha o aumento tumoral (grau 1 - 28,5%, grau 2 - 57,1% e grau 3 - 83,3%). E nos tumores de base, a maioria foi de meningiomas grau 1 (71,4%). Uma expressão elevada do gene HNRNPU (média em cada grupo - 11.735,94, 2.822,48 e 27.431,56 folds); apenas a diferença das médias entre os graus 2 e 3 apresentaram "significância" (modelo simples: -24.542,6; modelo múltiplo: -25.884,41). Foi realizada um curva ROC (gene HNRNPU) entre os meningiomas graus 2 e 3, com uma sensibilidade e especificidade de 80%, foi identificado o valor 5679,36 folds. Conclusões: O gene HNRNPU apresenta uma potencial ferramenta molecular no auxílio da distinção diagnóstica entre meningiomas grau 2 e 3.
Title in English
Expression of miR-27a, miR-216a and HNRNPU gene microRNAs in meningiomas and their correlations with tumor progression
Keywords in English
Expression profile
Meningiomas
microRNAs
Tumor progression
Abstract in English
Introduction: Meningiomas are slow-growing intracranial neoplasms that originate from arachnoid meningothelial cells and represent more than 33% of primary tumors of the central nervous system. They are a great challenge in their management. The most effective and recommended treatment is maximum surgical resection, without compromising the neurological function of the patient. Extremely frequent neoplasia, scarce adjunctive treatment options, and poorly understood at the molecular level culminate in a challenging environment of paramount medical importance for new therapies to emerge and provide the best treatment for patients. In this context, the role of microRNAs, which are non-coding RNAs (ncRNAs) consisting of 19 to 25 nucleotides, whose function is the silencing of mRNA at the post-transcriptional level, has been highlighted. Therefore, the aim of our study was to evaluate tissue and plasma expression of miR-27a, miR-216a and HNRNPU gene. Patients and methods: The miRNAs miR-27a, miR-216a, and HNRNPU gene were selected from our group's previous study by the large-scale microarray analysis technique, where grade I meningiomas were compared with control arachnoid samples. In this work, the expression of these miRNAs (tumor tissue and plasma) and the HNRNPU gene were evaluated by real-time PCR in grade I, II and III meningiomas, respectively with 14, 14 and 6 patients. Results: The mean age was 55 years, 76.5% (26) of women and 23.5% (8) men. There was a progressive increase in the proportion of males as the tumor grade rises (grade 1 - 7.1%, grade 2 - 28.6%, and grade 3 - 50%). The proportion of convexity meningiomas accompanies tumor enlargement (grade 1 - 28.5%, grade 2 - 57.1% and grade 3 - 83.3%). And in the base tumors, most were grade 1 meningiomas (71.4%). There were a high expression of the HNRNPU gene (mean in each group - 11,735.94, 2,822.48 and 27,431.56 folds); only the difference in the means between grades 2 and 3 showed statistical significance (simple model: - 24,542.6; multiple model: -25,884.41). A ROC curve (HNRNPU gene) was performed between grade 2 and 3 meningiomas, with a sensitivity and specificity of 80%, and a value of 5679.36 folds was identified. Conclusions: The HNRNPU gene presents a potential molecular tool to aid in the diagnostic distinction between grade 2 and 3 meningiomas.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2020-07-10
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2022. All rights reserved.