title: MYU, a Target lncRNA for Wnt/c-Myc Signaling, Mediates Induction of CDK6 to Promote Cell Cycle Progression.
abstract: Aberrant activation of Wnt/β-catenin signaling is a major driving force in colon cancer. Wnt/β-catenin signaling induces the expression of the transcription factor c-Myc, leading to cell proliferation and tumorigenesis. c-Myc regulates multiple biological processes through its ability to directly modulate gene expression. Here, we identify a direct target of c-Myc, termed MYU, and show that MYU is upregulated in most colon cancers and required for the tumorigenicity of colon cancer cells. Furthermore, we demonstrate that MYU associates with the RNA binding protein hnRNP-K to stabilize CDK6 expression and thereby promotes the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signaling and plays a critical role in the proliferation and tumorigenicity of colon cancer cells.
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address: kawasaki@iam.u-tokyo.ac.jp.
authors: Yoshihiro
authors: Y
authors: Kawasaki
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Mimon
authors: M
authors: Komiya
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Kosuke
authors: K
authors: Matsumura
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Lumi
authors: L
authors: Negishi
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Sakiko
authors: S
authors: Suda
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Masumi
authors: M
authors: Okuno
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Naoko
authors: N
authors: Yokota
authors: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Tomoya
authors: T
authors: Osada
authors: Laboratory for Cellular Systems Modeling, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Takeshi
authors: T
authors: Nagashima
authors: Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Masaya
authors: M
authors: Hiyoshi
authors: Laboratory for Cellular Systems Modeling, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors: Mariko
authors: M
authors: Okada-Hatakeyama
authors: Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Joji
authors: J
authors: Kitayama
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, 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, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address: akiyama@iam.u-tokyo.ac.jp.
authors: Tetsu
authors: T
authors: Akiyama
mesh_terms: D000818:Animals; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; C000624703:long non-coding RNA MYU, human; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6