Downregulation of bcl-2 expression in lymphoma cells by bcl-2 ARE-targeted modified, synthetic ribozyme.
Cancer Gene Ther
; 10(3): 201-8, 2003 Mar.
Article
em En
| MEDLINE
| ID: mdl-12637941
ABSTRACT
Synthetic ribozymes are catalytic RNA molecules designed to inhibit gene expression by cleaving specific mRNA sequences. We investigated the potential of synthetic ribozymes to inhibit bcl-2 expression in apoptosis defective bcl-2 overexpressing tumors. A chemically stabilized hammerhead ribozyme has been targeted to the A+U-rich regulative element of bcl-2 mRNA that is involved in bcl-2 gene switch-off during apoptosis. The design of the ribozyme was based on the results of probing accessibility of the RNA target in cellular extracts with antisense DNA. The ribozyme was lipotransfected to a bcl-2 overexpressing human lymphoma cell line (Raji). The cellular uptake of this ribozyme resulted in a marked reduction of both bcl-2 mRNA and BCL-2 protein levels and dramatically increased cellular death by apoptosis. Our results suggest a potential therapeutic application of such ribozyme for the treatment of bcl-2 overexpressing tumors.
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Base de dados:
MEDLINE
Assunto principal:
RNA Catalítico
/
Linfoma de Burkitt
/
Proteínas Proto-Oncogênicas c-bcl-2
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article