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ß-Catenin Regulates Multiple Steps of RNA Metabolism as Revealed by the RNA Aptamer in Colon Cancer Cells

¹ Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University and ² Department of Chemistry and Education, Seoul National University, Seoul, Republic of Korea

Requests for reprints: Sunjoo Jeong, Department of Molecular Biology, Dankook University, Seoul, Republic of Korea. Phone: 82-2-709-2819; Fax: 82-2-793-0176; E-mail: sjsj{at}dankook.ac.kr.

Nuclear ß-catenin forms a transcription complex with TCF-4, which is implicated in colon cancer development and progression. Recently, we and others have shown that ß-catenin could be a regulator of RNA splicing and it also stabilizes the cyclooxygenase-2 (COX-2) mRNA. Here, we further explored the role of ß-catenin in the RNA metabolism in colon cancer cells. To specifically modulate the subcellular functions of ß-catenin, we expressed the RNA aptamer in the form of RNA intramers with unique cellular localizations. The nucleus-expressed RNA intramer proved to be effective in reducing the protein-protein interaction between ß-catenin and TCF-4, thus shown to be a specific regulator of ß-catenin–activated transcription. It could also regulate the alternative splicing of E1A minigene in diverse colon cancer cell lines. In addition, we tested whether ß-catenin could stabilize any other mRNAs and found that cyclin D1 mRNA was also bound and stabilized by ß-catenin. Significantly, the cytoplasm-expressed RNA intramer reverted the ß-catenin–induced COX-2 and cyclin D1 mRNA stabilization. We show here that ß-catenin regulated multiple steps of RNA metabolism in colon cancer cells and might be the protein factor coordinating RNA metabolism. We suggest that the RNA intramers could provide useful ways for inhibiting ß-catenin–mediated transcription and RNA metabolism, which might further enhance the antitumorigenic effects of these molecules in colon cancer cells. [Cancer Res 2007;67(19):9315–20]

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