title: ASBEL-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)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.ASBELinteracts with and recruits TCF3 to the activating transcription factor 3 (ATF3) locus, where it represses the expression of ATF3. Furthermore, we demonstrate thatASBEL-TCF3-mediated down-regulation of ATF3 expression is required for the proliferation and tumorigenicity of colon tumor cells. ATF3, in turn, represses the expression ofASBELOur 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.
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Kenzui
authors: K
authors: Taniue
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.|Oncology Research Laboratories, Daiichi Sankyo Co., Ltd, Shinagawa-ku, Tokyo 140-8710, Japan.
authors: Akiko
authors: A
authors: Kurimoto
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Yasuko
authors: Y
authors: Takeda
authors: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Takeshi
authors: T
authors: Nagashima
authors: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Mariko
authors: M
authors: Okada-Hatakeyama
authors: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Yuki
authors: Y
authors: Katou
authors: Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan; akiyama@iam.u-tokyo.ac.jp.
authors: Tetsu
authors: T
authors: Akiyama
keywords: ASBEL; ATF3; colorectal tumorigenesis; noncoding RNA; β-catenin