SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

Nkerorema Djodji Damas; Michela Marcatti; Christophe Côme; Lise-Lotte Christensen; Morten Muhlig Nielsen; Roland Baumgartner; Helene Maria Gylling; Giulia Maglieri; Carsten Friis Rundsten; Ernst Stefan Seemann; Nicolas Rapin; Simon Thézenas; Søren Vang; Torben Ørntoft; Claus Lindbjerg Andersen; Jakob Skou Pedersen; Anders H Lund

doi:10.1038/ncomms13875

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

Nkerorema Djodji Damas, Michela Marcatti, Christophe Côme, Lise-Lotte Christensen, Morten Muhlig Nielsen, Roland Baumgartner, Helene Maria Gylling, Giulia Maglieri, Carsten Friis Rundsten, Ernst Stefan Seemann, Nicolas Rapin, Simon Thézenas, Søren Vang, Torben Ørntoft, Claus Lindbjerg Andersen, Jakob Skou Pedersen, Anders H Lund

Bioinformatik og RNA Biologi

122 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	13875
Tidsskrift	Nature Communications
Vol/bind	7
Antal sider	14
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms13875
Status	Udgivet - 22 dec. 2016

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10.1038/ncomms13875Licens: CC BY

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilizationForlagets udgivne version, 1,37 MBLicens: CC BY

Citationsformater

Damas, N. D., Marcatti, M., Côme, C., Christensen, L.-L., Nielsen, M. M., Baumgartner, R., Gylling, H. M., Maglieri, G., Rundsten, C. F., Seemann, E. S., Rapin, N., Thézenas, S., Vang, S., Ørntoft, T., Andersen, C. L., Pedersen, J. S., & Lund, A. H. (2016). SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization. Nature Communications, 7, Artikel 13875. https://doi.org/10.1038/ncomms13875

Damas, ND, Marcatti, M, Côme, C, Christensen, L-L, Nielsen, MM, Baumgartner, R, Gylling, HM, Maglieri, G, Rundsten, CF , Seemann, ES, Rapin, N, Thézenas, S, Vang, S, Ørntoft, T, Andersen, CL, Pedersen, JS & Lund, AH 2016, 'SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization', Nature Communications, bind 7, 13875. https://doi.org/10.1038/ncomms13875

@article{634c590db4f8474a81077243fdddf0f7,

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.",

author = "Damas, {Nkerorema Djodji} and Michela Marcatti and Christophe C{\^o}me and Lise-Lotte Christensen and Nielsen, {Morten Muhlig} and Roland Baumgartner and Gylling, {Helene Maria} and Giulia Maglieri and Rundsten, {Carsten Friis} and Seemann, {Ernst Stefan} and Nicolas Rapin and Simon Th{\'e}zenas and S{\o}ren Vang and Torben {\O}rntoft and Andersen, {Claus Lindbjerg} and Pedersen, {Jakob Skou} and Lund, {Anders H}",

year = "2016",

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doi = "10.1038/ncomms13875",

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TY - JOUR

T1 - SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

AU - Damas, Nkerorema Djodji

AU - Marcatti, Michela

AU - Côme, Christophe

AU - Christensen, Lise-Lotte

AU - Nielsen, Morten Muhlig

AU - Baumgartner, Roland

AU - Gylling, Helene Maria

AU - Maglieri, Giulia

AU - Rundsten, Carsten Friis

AU - Seemann, Ernst Stefan

AU - Rapin, Nicolas

AU - Thézenas, Simon

AU - Vang, Søren

AU - Ørntoft, Torben

AU - Andersen, Claus Lindbjerg

AU - Pedersen, Jakob Skou

AU - Lund, Anders H

PY - 2016/12/22

Y1 - 2016/12/22

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms13875

DO - 10.1038/ncomms13875

M3 - Journal article

C2 - 28004750

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 13875

ER -

SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization

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