title: Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1.
abstract: Many long noncoding RNAs (lncRNAs) are reported to be dysregulated in human cancers and play critical roles in tumor development and progression. Furthermore, it has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic loci or by controlling transcriptional or posttranscriptional processes. Here we show that an lncRNA termed UPAT [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domain-containing protein 1 (UHRF1) Protein Associated Transcript] is required for the survival and tumorigenicity of colorectal cancer cells. UPAT interacts with and stabilizes the epigenetic factor UHRF1 by interfering with its β-transducin repeat-containing protein (TrCP)-mediated ubiquitination. Furthermore, we demonstrate that UHRF1 up-regulates Stearoyl-CoA desaturase 1 and Sprouty 4, which are required for the survival of colon tumor cells. Our study provides evidence for an lncRNA that regulates protein ubiquitination and degradation and thereby plays a critical role in the survival and tumorigenicity of tumor cells. Our results suggest that UPAT and UHRF1 may be promising molecular targets for the therapy of colon cancer.
authors.affiliation: 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.forename: Kenzui
authors.initials: K
authors.lastname: Taniue
authors.affiliation: 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; Oncology Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan;
authors.forename: Akiko
authors.initials: A
authors.lastname: Kurimoto
authors.affiliation: 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.forename: Hironobu
authors.initials: H
authors.lastname: Sugimasa
authors.affiliation: 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.forename: Emiko
authors.initials: E
authors.lastname: Nasu
authors.affiliation: 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.forename: Yasuko
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: 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.forename: Kei
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Department of Cell Proliferation, United Center for Advanced Research and Translational Medicine, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-0872, Japan;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan;
authors.forename: Mariko
authors.initials: M
authors.lastname: Okada-Hatakeyama
authors.affiliation: Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan;
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oyama
authors.affiliation: Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan;
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kozuka-Hata
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Hiyoshi
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.affiliation: 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.forename: Lumi
authors.initials: L
authors.lastname: Negishi
authors.affiliation: 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.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: 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; akiyama@iam.u-tokyo.ac.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D059748:Proteolysis; D062085:RNA, Long Noncoding / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; C499038:SPRY4 protein, human; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D008239:Lysine
keywords: UHRF1; UPAT; long noncoding RNA; tumorigenicity; ubiquitination