RT Journal Article
SR Electronic
T1 Increased Bcl2 Expression by Antisense Oligoribonucleotides Targeting the Adenine-Uridine-Rich Element Motif
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 816
OP 821
DO 10.1124/mol.105.014357
VO 68
IS 3
A1 Laura Ghisolfi
A1 Laura Papucci
A1 Annamaria Bevilacqua
A1 Gianfranco Canti
A1 Giuseppe Tataranni
A1 Andrea Lapucci
A1 Nicola Schiavone
A1 Sergio Capaccioli
A1 Angelo Nicolin
YR 2005
UL http://molpharm.aspetjournals.org/content/68/3/816.abstract
AB 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 half-life 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.