Construction of a novel DNA decoy that inhibits the oncogenic beta-catenin/T-cell factor pathway

Molecular Cancer Therapeutics
Yosuke SekiMorito Monden

Abstract

The oncogenic beta-catenin/T-cell factor (TCF) signal is a common trigger inducing expressions of various cancer-related genes and is activated in various types of human malignancy. The aim of this study was to create an effective double-stranded DNA decoy that would interfere with endogenous TCF hyperactivity in tumor cells. We first established the TCF-activated model using nontumor human embryonic kidney 293 (HEK293) cells by introducing a beta-catenin cDNA. Based on a consensus TCF-binding sequence in the cyclin D1 and c-myc promoters, several double-stranded oligodeoxynucleotides were designed and tested for their ability to inhibit TCF activity in the HEK293 model. Among them, the 18-mer oligodeoxynucleotide stably formed double-stranded DNA and efficiently inhibited TCF activity. FITC-labeled oligodeoxynucleotide was efficiently incorporated into the nucleus at 6 hours and remained within cells for up to 72 to 96 hours. When compared with scrambled oligodeoxynucleotide, we found that the 18-mer TCF decoy significantly inhibited TCF activity and promoter activities of the downstream target genes, such as cyclin D1, c-myc, and matrix metalloproteinase 7 in HCT116 colon cancer cells. Reverse transcription-PCR assays indicat...Continue Reading

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Citations

Oct 29, 2008·Evidence-based Complementary and Alternative Medicine : ECAM·Kourt ChatelainKarl Kingsley
Apr 28, 2010·Environmental Health Perspectives·Shota TakumiToru Takeuchi
Mar 29, 2014·Journal of Dietary Supplements·Javid OsafiKarl Kingsley
Aug 29, 2006·Seminars in Cancer Biology·Marina Vita, Marie Henriksson
Jun 20, 2018·Molecular Medicine Reports·Zhenguang DuShaonian Xu
Aug 15, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Noha S AhmedSavita Khanna

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