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PLoS One ; 11(12): e0168229, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28005927

RESUMO

INTRODUCTION: MicroRNAs are essential regulators of gene expression at the post-transcriptional level. Their expression is altered in cancer tissues, and evaluation of these alterations is considered a promising tool used to diagnose and identify prognostic markers. MATERIALS AND METHODS: The microRNA expression profiles of formalin-fixed, paraffin-embedded melanoma and melanocytic nevi samples were estimated with a microarray and subsequently validated by real-time PCR. Melanoma cells were transfected with miR-4286 inhibitor to evaluate the influence of this microRNA on the viability, proliferation, apoptosis, migration, and invasion of melanoma cells. RESULTS: The microarray revealed that the expression of 1,171 microRNAs was altered in melanoma samples compared to melanocytic nevi. Real-time PCR validation experiments found the microRNA expression levels to correspond to the melanoma/melanocytic nevi microarray results. The pathway analysis identified 52 modulated pathways in melanoma. Moreover, the application of miR-4286 inhibitor to BRO melanoma cells resulted in a 2.6-fold increase in the apoptosis rate and a 1.7-fold decrease in the cell proliferation/viability but did not affect the invasiveness and migration of these cells. Furthermore, the use of miR-4286 inhibitor altered the mRNA expression of several miR-4286 gene targets: folylpolyglutamate synthase, RNA polymerase I-specific transcription initiation factor, apelin, G-protein-coupled receptor 55, and high-mobility group A1 protein, which have been implicated in cell proliferation/apoptosis regulation. Lastly, the transiently transfected SK-MEL-1 cells with miR-4286 inhibitor decreased proliferation rate and modulated folylpolyglutamate synthase rates of these cells. CONCLUSION: Our results demonstrate that miR-4286 mediates proliferation and apoptosis in melanoma cells, these findings may represent a novel mechanism underlying these processes.


Assuntos
Apoptose , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Melanoma/patologia , MicroRNAs/genética , Nevo Pigmentado/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Movimento Celular , Feminino , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Nevo Pigmentado/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Análise Serial de Tecidos , Células Tumorais Cultivadas
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