title: Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer.
abstract: T-cell factor (TCF)-1 protein forms the transcriptional complex with beta-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/beta-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/beta-catenin transcription activity as shown by luciferase assay. It also modulated the expression of TCF/beta-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/beta-catenin-mediated carcinogenesis.
authors.affiliation: Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University, Hannam-dong san 8, Yongsan-ku, Seoul 140-714, Korea.
authors.forename: Kang Hyun
authors.initials: KH
authors.lastname: Choi
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Park
authors.forename: Seung Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Mi-Ya
authors.initials: MY
authors.lastname: Jeon
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Hee Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Yu
authors.forename: Hong-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyungsook
authors.initials: K
authors.lastname: Han
authors.forename: Heviran
authors.initials: H
authors.lastname: Lee
authors.forename: Keerang
authors.initials: K
authors.lastname: Park
authors.forename: Woong June
authors.initials: WJ
authors.lastname: Park
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
mesh_terms: D052157:Aptamers, Nucleotide / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D048708:Cell Growth Processes / Q000235:genetics; D015870:Gene Expression; D045325:HCT116 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D051822:T Cell Transcription Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D051822:T Cell Transcription Factor 1; D051176:beta Catenin