title: SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization.
abstract: We currently have limited knowledge of the involvement of long non-coding RNAs (lncRNAs) in normal cellular processes and pathologies. Here, we identify and characterize SNHG5 as a stable cytoplasmic lncRNA with up-regulated expression in colorectal cancer. Depletion of SNHG5 induces cell cycle arrest and apoptosis in vitro and limits tumour outgrowth in vivo, whereas SNHG5 overexpression counteracts oxaliplatin-induced apoptosis. Using an unbiased approach, we identify 121 transcript sites interacting with SNHG5 in the cytoplasm. Importantly, knockdown of key SNHG5 target transcripts, including SPATS2, induces apoptosis and thus mimics the effect seen following SNHG5 depletion. Mechanistically, we suggest that SNHG5 stabilizes the target transcripts by blocking their degradation by STAU1. Accordingly, depletion of STAU1 rescues the apoptosis induced after SNHG5 knockdown. Hence, we characterize SNHG5 as a lncRNA promoting tumour cell survival in colorectal cancer and delineate a novel mechanism in which a cytoplasmic lncRNA functions through blocking the action of STAU1.
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Nkerorema Djodji
authors.initials: ND
authors.lastname: Damas
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Michela
authors.initials: M
authors.lastname: Marcatti
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Christophe
authors.initials: C
authors.lastname: Côme
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Christensen
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
authors.forename: Morten Muhlig
authors.initials: MM
authors.lastname: Nielsen
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Roland
authors.initials: R
authors.lastname: Baumgartner
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Helene Maria
authors.identifier: http://orcid.org/0000-0002-6875-2845
authors.initials: HM
authors.lastname: Gylling
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Giulia
authors.initials: G
authors.lastname: Maglieri
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Carsten Friis
authors.initials: CF
authors.lastname: Rundsten
authors.affiliation: Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3 1870, Frederiksberg, Denmark.
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Seemann
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rapin
authors.affiliation: Biostatistics Unit, Institut Régional du Cancer de Montpellier (ICM)-Val d'Aurelle, 208 Avenue des Apothicaires, 34298 Montpellier, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Thézenas
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Vang
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Ørntoft
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
authors.forename: Claus Lindbjerg
authors.initials: CL
authors.lastname: Andersen
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
authors.forename: Jakob Skou
authors.identifier: http://orcid.org/0000-0002-7236-4001
authors.initials: JS
authors.lastname: Pedersen
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
authors.forename: Anders H
authors.identifier: http://orcid.org/0000-0002-7407-3398
authors.initials: AH
authors.lastname: Lund
mesh_terms: D017209:Apoptosis; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D003598:Cytoskeletal Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C486737:SPATS2 protein, human; C492185:STAU1 protein, human; C000611749:long non-coding RNA SNHG5, human