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Molecular Pharmacology Fast Forward
First published on June 13, 2005; DOI: 10.1124/mol.105.014357

0026-895X/05/6803-816-821$20.00
Mol Pharmacol 68:816-821, 2005

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Increased Bcl2 Expression by Antisense Oligoribonucleotides Targeting the Adenine-Uridine-Rich Element Motif

Laura Ghisolfi, Laura Papucci, Annamaria Bevilacqua, Gianfranco Canti, Giuseppe Tataranni, Andrea Lapucci, Nicola Schiavone, Sergio Capaccioli, and Angelo Nicolin

Department of Pharmacology, University of Milan, Milan, Italy (L.G., A.B., G.C., G.T., A.N.); and Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy (L.P., A.L., N.S., S.C.)

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.

Received April 29, 2005; accepted June 13, 2005

Address correspondence to: Dr. Angelo Nicolin, Department of Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. E-mail: angelo.nicolin{at}unimi.it




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