Use of RNA Aptamers for the Modulation of Cancer Cell Signaling
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/β-catenin signaling pathway plays important roles in a critical initiating event in the formation of various human cancers. Because mutations in β-catenin have been found to be responsible for human tumorigenesis, β-catenin is the molecular target for effective anticancer therapies. Here, we describe the selection of RNA aptamers against β-catenin/transcription factor (TCF) proteins and their intracellular expression as intramers. The RNA aptamers acted as central inhibitory players for multiple oncogenic functions of β-catenin in colon cancer cells. These data provide the proof-of-principle for the use of RNA aptamers for an effective anticancer gene therapy.
KeywordsAnticancer therapy β-catenin colon cancer RNA aptamer RNA intramer TCF tumorigenesis
This study was supported by grants from the Korea Research Foundation, the Korea Science and Engineering Foundation, the Korean Ministry of Sciences and Technology, and the Korean Ministry of Health and Welfare.
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