1. ASBEL –TCF3 complex is required for the tumorigenicity of colorectal cancer cells
- Author
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Kenzui Taniue, Takeshi Nagashima, Tetsu Akiyama, Mariko Okada-Hatakeyama, Yuki Katou, Katsuhiko Shirahige, Akiko Kurimoto, and Yasuko Takeda
- Subjects
0301 basic medicine ,ATF3 ,Multidisciplinary ,Colorectal cancer ,Wnt signaling pathway ,Activating transcription factor ,Biological Sciences ,Biology ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,Transcription (biology) ,TCF3 ,embryonic structures ,Cancer research ,medicine ,Carcinogenesis ,Transcription factor - Abstract
Wnt/β-catenin signaling plays a key role in the tumorigenicity of colon cancer. Furthermore, it has been reported that lncRNAs are dysregulated in several steps of cancer development. Here we show that β-catenin directly activates the transcription of the long noncoding RNA (lncRNA) ASBEL [antisense ncRNA in the ANA (Abundant in neuroepithelium area)/BTG3 (B-cell translocation gene 3) locus] and transcription factor 3 (TCF3), both of which are required for the survival and tumorigenicity of colorectal cancer cells. ASBEL interacts with and recruits TCF3 to the activating transcription factor 3 (ATF3) locus, where it represses the expression of ATF3. Furthermore, we demonstrate that ASBEL-TCF3-mediated down-regulation of ATF3 expression is required for the proliferation and tumorigenicity of colon tumor cells. ATF3, in turn, represses the expression of ASBEL Our results reveal a pathway involving an lncRNA and two transcription factors that plays a key role in Wnt/β-catenin-mediated tumorigenesis. These results may provide insights into the variety of biological and pathological processes regulated by Wnt/β-catenin signaling.
- Published
- 2016