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
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13875
ER -