Modulation of oncogenic transcription and alternative splicing by beta-catenin and an RNA aptamer in colon cancer cells.
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.
Lee
Hee Kyu
HK
BK21 Graduate Program for RNA Biology, Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul, Republic of Korea.
Choi
Yong Seok
YS
Park
Young Ae
YA
Jeong
Sunjoo
S
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*
D052157:Aptamers, Nucleotide; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D051176:beta Catenin