<i>ASBEL</i>-TCF3 complex is required for the tumorigenicity of colorectal cancer cells.

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) <i>ASBEL</i> [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. <i>ASBEL</i> interacts with and recruits TCF3 to the activating transcription factor 3 (<i>ATF3</i>) locus, where it represses the expression of ATF3. Furthermore, we demonstrate that <i>ASBEL</i>-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 <i>ASBEL</i> 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.