Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer

T-cell factor (TCF)-1 protein forms the transcriptional complex with β-catenin and regulates the expression of diverse target genes during early development and carcinogenesis. We have selected previously an RNA aptamer that binds to the DNA-binding domain of TCF-1 and have shown that it interfered...

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Published in:Molecular cancer therapeutics 2006-09, Vol.5 (9), p.2428-2434
Main Authors: Choi, Kang Hyun, Park, Min Woo, Lee, Seung Yeon, Jeon, Mi-Ya, Kim, Mee Young, Lee, Hee Kyu, Yu, Jaehoon, Kim, Hong-Jin, Han, Kyungsook, Lee, Heviran, Park, Keerang, Park, Woong June, Jeong, Sunjoo
Format: Article
Language:English
Subjects:
Aptamers, Nucleotide - biosynthesis
Aptamers, Nucleotide - genetics
Base Sequence
beta Catenin - genetics
beta Catenin - metabolism
Cell Growth Processes - genetics
cyclin D1
Gene Expression
HCT116 Cells
Humans
intramer
Molecular Sequence Data
Nucleic Acid Conformation
RNA aptamer
T Cell Transcription Factor 1 - biosynthesis
T Cell Transcription Factor 1 - genetics
TCF-1
Transcription, Genetic
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Summary:T-cell factor (TCF)-1 protein forms the transcriptional complex with β-catenin and regulates the expression of diverse target genes during early development and carcinogenesis. We have selected previously an RNA aptamer that binds to the DNA-binding domain of TCF-1 and have shown that it interfered with binding of TCF-1 to its specific DNA recognition sequences in vitro . As an approach to modulate the transcription by TCF/β-catenin complex in the cells, we have developed the RNA expression vector for stable expression of RNA aptamer inside of the mammalian cells. High level of RNA was expressed as an intramer in the fusion with the stable RNA transcript. The RNA intramer inhibited TCF/β-catenin transcription activity as shown by luciferase assay. It also modulated the expression of TCF/β-catenin target genes, such as cyclin D1 and matrix metalloproteinase-7, as predicted to be as an effective inhibitor of the TCF function. In addition, it efficiently reduced the growth rate and tumorigenic potential of HCT116 colon cancer cells. Such RNA intramer could lead to valuable gene therapeutics for TCF/β-catenin-mediated carcinogenesis. [Mol Cancer Ther 2006;5(9):2428–34]
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-05-0204