Use of RNA Aptamers for the Modulation of Cancer Cell Signaling

Abstract

Aptamers are in vitro evolved molecules that bind to target proteins with high affinity and specificity by adapting three-dimensional structures upon binding. Because cancer cells exhibit the activation of signaling pathways that are not usually activated in normal cells, RNA aptamers against such a cancer cell-specific signal can be useful lead molecules for cancer gene therapy. The Wnt/beta-catenin signaling pathway plays important roles in a critical initiating event in the formation of various human cancers. Because mutations in beta-catenin have been found to be responsible for human tumorigenesis, beta-catenin is the molecular target for effective anticancer therapies. Here, we describe the selection of RNA aptamers against beta-catenin/T-Cell Factor (TCF) proteins and their intracellular expression as intramers. The RNA aptamers acted as central inhibitory players for multiple oncogenic functions of beta-catenin in colon cancer cells. These data provide the proof-of-principle for the use of RNA aptamers for an effective anticancer gene therapy.