Increased Bcl2 expression by antisense oligoribonucleotides targeting the adenine-uridine-rich element motif

Mol Pharmacol. 2005 Sep;68(3):816-21. doi: 10.1124/mol.105.014357. Epub 2005 Jun 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / metabolism*
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • Gene Expression Regulation / drug effects*
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Antisense / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Uridine / metabolism*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Antisense
  • Adenine
  • Uridine