RNA has become a promising target for pharmacological purposes. Most current strategies are directed toward down-regulating its functions. In this study, we provide evidence of the up-regulation of messenger RNA in a sequence-specific manner. The bcl2 (b)-ARE (adenine-uridine-rich element) in the 3'-untranslated region of the b-RNA that regulates the rate of RNA degradation has been targeted with three chemically modified oligoribonucleotides designed in the antisense orientation (asORNs). The three asORNs were studied by a cell-free degradation assay. All three slowed the rate of RNA decay in a dose-response fashion, they were specific to the b-ARE, and two of them were individually effective. asORNs were then transfected into the malignant cells in culture and b-RNA halflife was measured by real-time reverse transcriptase-polymerase chain reaction. We showed that by stabilizing b-RNA the three asORNs increased the expression of b-RNA and of the relevant protein in a dose-response fashion. Copyright (copyright) 2005 The American Society for Pharmacology and Experimental Therapeutics.
Increased bcl2 expression by antisense oligoribonucleotides targeting the adenine-uridine-rich element motif / L. Ghisolfi, A. Nicolin, L. Papucci, A. Bevilacqua, G. Canti, G. Tataranni, A. Lapucci, N. Schiavone, S. Capaccioli. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - 68:3(2005), pp. 816-821.
|Titolo:||Increased bcl2 expression by antisense oligoribonucleotides targeting the adenine-uridine-rich element motif|
GHISOLFI, LAURA (Primo)
NICOLIN, ANGELO NICOLO' (Secondo)
|Parole Chiave:||3' untranslated region ; RNA degradation ; article ; controlled study ; drug mechanism ; gene overexpression ; genetic transfection ; human cell ; human ; priority journal ; protein expression ; protein motif ; upregulation ; adenine ; antisense oligonucleotide ; protein bcl 2 ; uridine|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1124/mol.105.014357|
|Appare nelle tipologie:||01 - Articolo su periodico|