Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation.
Biochem Biophys Res Commun
; 461(2): 329-33, 2015 May 29.
Article
em En
| MEDLINE
| ID: mdl-25888794
Epigenetic inactivation of genes plays a critical role in many important human diseases, especially in cancer. A core mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA, which is catalyzed by DNA methyltransferases (DNMTs). The inhibition of DNMTs may lead to demethylation and expression of the silenced tumor suppressor genes. Although DNMT inhibitors are currently being developed as potential anticancer agents, only limited success is achieved due to substantial toxicity. Here, we utilized a multiplex selection system to generate efficient RNA-cleaving DNAzymes targeting DNMT1. The lead molecule from the selection was shown to possess efficient kinetic profiles and high efficiency in inhibiting the enzyme activity. Transfection of the DNAzyme caused significant down-regulation of DNMT1 expression and reactivation of p16 gene, resulting in reduced cell proliferation of bladder cancers. This study provides an alternative for targeting DNMTs for potential cancer therapy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bexiga Urinária
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Neoplasias da Bexiga Urinária
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DNA Catalítico
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DNA (Citosina-5-)-Metiltransferases
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article