lncRNA ASBEL-TCF3 complex is required for the tumorigenicity of colorectal cancer cells

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 researchers from the University of Tokyo 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, the researchers 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.

Transactivation of ASBEL and TCF3 by β-catenin is required
for β-catenin–mediated proliferation of colon cancer cells

lncRNA

(A) Depiction of a screen to identify β-catenin target genes. (B) qRT-PCR analysis of the expression of the indicated genes in DLD-1 cells transfected with an siRNA targeting β-catenin or a control siRNA (siCont). Two distinct siRNAs targeting β-catenin (siβ-catenin #1 and #2) were used. Results are expressed as the mean ± SD (n = 3). *P < 0.05. (C) qRT-PCR analysis of the expression of the indicated genes in 293FT cells transfected with an siRNA targeting APC. Results are expressed as the mean ± SD (n = 3). *P < 0.05. (D) ChIP assays were performed with DLD-1 cells using anti–β-catenin antibody. The promoter region of AXIN2 was amplified as a positive control. The regions around −3,500 bp of ASBEL and −3,500 bp of TCF3 were amplified as negative controls. Results are expressed as the mean ± SD (n = 3). *P < 0.05. (E) ChIP assays were performed with 293FT cells transfected with an siRNA targeting APC (siAPC) using anti–β-catenin antibody. The promoter region of AXIN2 was amplified as a positive control. The regions around −3,500 bp of ASBEL and −3,500 bp of TCF3 were amplified as negative controls. Results are expressed as the mean ± SD (n = 3). *P < 0.05.

These results may provide insights into the variety of biological and pathological processes regulated by Wnt/β-catenin signaling.

Taniue K, Kurimoto A, Takeda Y, Nagashima T, Okada-Hatakeyama M, Katou Y, Shirahige K, Akiyama T. (2016) ASBEL-TCF3 complex is required for the tumorigenicity of colorectal cancer cells. Proc Natl Acad Sci U S A [Epub ahead of print]. [abstract]

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