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Doctoral Thesis
DOI
Document
Author
Full name
Agnes Assao
Institute/School/College
Knowledge Area
Date of Defense
Published
Bauru, 2019
Supervisor
Committee
Oliveira, Denise Tostes (President)
Camillo, Cláudia Malheiros Coutinho
Neves, Lucimara Teixeira das
Tjioe, Kellen Cristine
Title in Portuguese
Análise da expressão de miRNAs em lesões potencialmente malignas e no câncer de lábio
Keywords in Portuguese
Câncer labial
MicroRNAs
Queilite
Abstract in Portuguese
Os miRNAs são pequenas moléculas não codificantes de RNA, cuja expressão desregulada vem sendo associada à progressão das lesões potencialmente malignas para o câncer de boca. O objetivo deste trabalho foi analisar a expressão dos miRNA-181b, miRNA-21, miRNA-31, e miRNA-345 nas queilites actínicas e nos carcinomas espinocelulares de lábio inferior, verificando se estes miRNAs podem ajudar a identificar o risco de transformação maligna e a evolução para o câncer. Foram selecionados, a partir de material emblocado em parafina, 19 queilites actínicas sem displasia epitelial, 32 queilites actínicas com displasia epitelial, 42 carcinomas espinocelulares de lábio inferior e 10 amostras de mucosa bucal com padrão de normalidade, provenientes da Faculdade de Medicina de Botucatu, UNESP e da Faculdade de Odontologia de Bauru, USP. A quantificação dos miRNAs nas amostras foi realizada por meio da reação de polimerase em cadeia, em tempo real (RT-PCR). A partir da diferença da expressão relativa de cada miRNA em relação ao epitélio labial normal, a expressão dos miRNAs foi classificada em aumentada, equivalente ou diminuída. A comparação quantitativa das expressões dos miRNAs analisados nas queilites actínicas com e sem displasia epitelial e nos carcinomas espinocelulares de lábio inferior, foi realizada pelo teste de Kruskal-Wallis, com nível de significância de 5%. Os resultados mostraram diferentes níveis de expressão dos miRNA-181b, miRNA-21, miRNA-31, e miRNA-345 no epitélio bucal das lesões investigadas. Houve uma expressão aumentada dos miRNA-181b, miRNA-31 e miRNA-345 na maioria das queilites actínicas sem displasia epitelial. Entretanto, nas queilites actínicas com displasia epitelial e nos CEC de lábio inferior, a expressão dos miRNA-181b, miRNA-31 e miRNA-345, foi equivalente àquela da mucosa bucal com padrão de normalidade. O aumento da expressão do miRNA-21 nos CEC de lábio inferior foi estatisticamente significativo (p=0,022) quando comparado às queilites actínicas com displasia epitelial. A partir desses resultados, conclui-se que os miRNA- 181b, miRNA-21, miRNA-31 e miRNA-345 são expressos no epitélio bucal da região de lábio e o aumento da expressão do miRNA-21 pode ajudar a identificar as queilites actínicas com displasia epitelial que apresentam um risco de evolução para o carcinoma espinocelular de lábio.
Title in English
MicroRNA expression in oral potentially malignant disorders and in lower lip cancer
Keywords in English
Cheilitis
Lip cancer
miRNA
Abstract in English
Micro-RNAs (miRNAs) are small non-coding RNAs, which expression has been associated with the progression of oral potentially malignant disorders to oral cancer. The aim of this study was to analyze the expression of miR-181b, miR-21, miR-31 and miR-345 in actinic cheilitis and lower lip squamous cell carcinomas, and to verify if these miRNAs can be helpful to determine the risk of malignant progression to oral cancer. The sample was selected from formalin-fixed paraffin embedded tissues of 19 actinic cheilitis without epithelial dysplasia, 32 actinic cheilitis with epithelial dysplasia, 42 lower lip squamous cell carcinomas and 10 normal oral mucosa, from the Bauru School of Dentistry (USP) and from the Botucatu School of Medicine (UNESP). Micro-RNA expression was quantified by real time polymerase chain reaction (RT-PCR). The differences between the relative miRNA expression in the sample and in the normal lip epithelium were obtained and classified according to these values in up-regulated, equivalent or down-regulated. The expression of the selected miRNAs in actinic cheilitis, with and without epithelial dysplasia, and in lower lip squamous cell carcinomas was statistically compared by Kruskal-Wallis test and p values lower than 0.05 were considered statistically significant. The results showed that different levels of miR-181b, miR-21, miR-31, e miR-345 were detected in the oral epithelium of actinic cheilitis and lower lip squamous cell carcinomas. The miR-181b, miR-31 and miR-345 were upregulated in most of the actinic cheilitis without epithelial dysplasia. However, the expression of miR-181b, miR-31 and miR-345 in actinic cheilitis with epithelial dysplasia and in lower lip cancer was equivalent to the normal oral mucosa. Additionally, the increased expression of miR-21 in lower lip squamous cell carcinomas was statistically significant (p=0.022) when compared to actinic cheilitis with epithelial dysplasia. Based on our results, we concluded that miR-181b, miR-21, miR-31 and miR-345 are expressed in oral epithelium of the lip region and that the up-regulation of miR-21 can be helpful to identify patients with actinic cheilitis presenting epithelial dysplasia and higher risk of progression to lip cancer.
 
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AgnesAssao_Rev.pdf (2.96 Mbytes)
Publishing Date
2019-11-27
 
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