Β-catenin regulates multiple steps of RNA metabolism as revealed by the RNA aptamer in colon cancer cells

• Published in: Cancer research (Chicago, Ill.) Vol. 67; no. 19; pp. 9315 - 9321
• Main Authors: HEE KYU LEE, HO YOON KWAK, HUR, Jung, IN AE KIM, JI SUN YANG, MIN WOO PARK, YU, Jaehoon, JEONG, Sunjoo
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2007
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Alternative Splicing; Animals; Antineoplastic agents; Aptamers, Nucleotide - genetics; Aptamers, Nucleotide - metabolism; beta Catenin - antagonists & inhibitors; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Cyclin D1 - biosynthesis; Cyclin D1 - genetics; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 - genetics; Gastroenterology. Liver. Pancreas. Abdomen; HCT116 Cells; Humans; Medical sciences; Mice; NIH 3T3 Cells; Pharmacology. Drug treatments; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; TCF Transcription Factors - metabolism; Transcription Factor 7-Like 2 Protein; Tumors; Colonic disease; Colon cancer; RNA; β Catenin; Digestive diseases; Intestinal disease; Aptamer; Malignant tumor; Pharmacokinetics; Metabolism; Tumor cell
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-07-1128

Nuclear beta-catenin forms a transcription complex with TCF-4, which is implicated in colon cancer development and progression. Recently, we and others have shown that beta-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 beta-catenin in the RNA metabolism in colon cancer cells. To specifically modulate the subcellular functions of beta-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 beta-catenin and TCF-4, thus shown to be a specific regulator of beta-catenin-activated transcription. It could also regulate the alternative splicing of E1A minigene in diverse colon cancer cell lines. In addition, we tested whether beta-catenin could stabilize any other mRNAs and found that cyclin D1 mRNA was also bound and stabilized by beta-catenin. Significantly, the cytoplasm-expressed RNA intramer reverted the beta-catenin-induced COX-2 and cyclin D1 mRNA stabilization. We show here that beta-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 beta-catenin-mediated transcription and RNA metabolism, which might further enhance the antitumorigenic effects of these molecules in colon cancer cells.