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Carcinogenesis ; 39(3): 389-396, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29432532

RESUMO

Gliomas are characterized by a malignant phenotype with proliferation, cell cycle arrest and invasion. To explore the biological consequences of epigenetically regulated miRNAs, we performed a microarray-based screening (whose expression was affected by 5-AZA treatment) followed by bisulfite sequencing validation. We found that miR-134 as an epigenetically regulated suppressor gene with prognostic value in gliomas. MicroRNA-134 was downregulated in high-grade gliomas, especially in GBM samples. Functional studies in vitro and in vivo in mouse models showed that overexpression of miR-134 was sufficient to reduce cell cycle arrest, cell proliferation and invasion. Target analysis and functional assays correlated the malignant phenotype with miR-134 target gene KRAS, an established upstream regulator of ERK and AKT pathways. Overall, our results highlighted a role for miR-134 in explaining the malignant phenotype of gliomas and suggested its relevance as a target to develop for early diagnostics and therapy.


Assuntos
Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Neoplasias Encefálicas/genética , Inativação Gênica , Glioma/genética , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo
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