title: Modulation of oncogenic transcription and alternative splicing by beta-catenin and an RNA aptamer in colon cancer cells.
abstract: Activated beta-catenin regulates the transcription of oncogenic target genes and is critical for tumorigenesis. Because nuclear functions are frequently coupled, we investigated whether it also has a role in alternative splicing of oncogenic genes. We showed that stabilized beta-catenin caused alternative splicing of estrogen receptor-beta pre-mRNA in colon cancer cells. To establish a direct role of beta-catenin in regulated splicing, we selected a high-affinity RNA aptamer that associated with beta-catenin in vivo. Nuclear localized aptamer inhibited beta-catenin-dependent transcription of cyclin D1 and c-myc in colon cancer cells; thus, cells stably expressing the aptamer exhibited cell cycle arrest and reduced tumor forming potential. Most significantly, the aptamer prevented the alternative splicing induced by stabilized beta-catenin. Taken together, our results establish that beta-catenin has an important role in both transcription and splicing, and that its action can be modulated by a high-affinity RNA aptamer. The RNA aptamer could be further developed as a specific inhibitor for cancer therapeutics.
authors.affiliation: BK21 Graduate Program for RNA Biology, Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul, Republic of Korea.
authors.forename: Hee Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Park
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
mesh_terms: D021581:Active Transport, Cell Nucleus; D017398:Alternative Splicing; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D047629:Estrogen Receptor beta / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D052157:Aptamers, Nucleotide; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D051176:beta Catenin