ASBEL–TCF3 complex is required for the tumorigenicity of colorectal cancer cells
Menée sur des lignées cellualires de cancer du côlon, cette étude met en évidence le rôle joué par un long ARN non codant (ASBEL) et un facteur de transcription (TCF3) dans le développement d'une tumeur
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.