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SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism.

  • Christensen LL Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: liselotte.christensen@clin.au.dk.
  • True K Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: Kirsten_true@hotmail.com.
  • Hamilton MP Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. Electronic address: mphamilt@bcm.edu.
  • Nielsen MM Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: morten.muhlig@clin.au.dk.
  • Damas ND Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. Electronic address: Nkerorema.Damas@bric.ku.dk.
  • Damgaard CK Department of Molecular Biology and Genetics, University of Aarhus, Denmark. Electronic address: ckd@mbg.au.dk.
  • Ongen H Department of Genetic Medicine and Development, Functional Population Genomics and Genetics of Complex Traits Lab, University of Geneva Medical School, Geneva, Switzerland. Electronic address: Halit.Ongen@unige.ch.
  • Dermitzakis E Department of Genetic Medicine and Development, Functional Population Genomics and Genetics of Complex Traits Lab, University of Geneva Medical School, Geneva, Switzerland. Electronic address: Emmanouil.Dermitzakis@unige.ch.
  • Bramsen JB Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: bramsen@clin.au.dk.
  • Pedersen JS Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: jakob.skou@clin.au.dk.
  • Lund AH Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. Electronic address: anders.lund@bric.ku.dk.
  • Vang S Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: vang@clin.au.dk.
  • Stribolt K Department of Pathology, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: katrine.stribolt@rm.dk.
  • Madsen MR Surgical Research Unit, Herning Regional Hospital, Herning, Denmark. Electronic address: mogmad@rm.dk.
  • Laurberg S Department of Surgery, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: soerlaur@rm.dk.
  • McGuire SE Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: Sean.McGuire@bcm.edu.
  • Ørntoft TF Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: orntoft@clin.au.dk.
  • Andersen CL Department of Molecular Medicine (MOMA), Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. Electronic address: cla@clin.au.dk.
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  • 2016-07-12
Published in:
  • Molecular oncology. - 2016
AGO-CLIP
Colorectal cancer
Functional analyses
Long non-coding RNAs
SNHG16
Wnt pathway
Apoptosis
Cell Movement
Cell Proliferation
Cell Survival
Colorectal Neoplasms
Cytoplasm
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HCT116 Cells
Humans
Lipid Metabolism
Nucleotide Motifs
Polyribosomes
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc
RNA, Long Noncoding
RNA, Small Nucleolar
Transcription Factors
Up-Regulation
Wnt Signaling Pathway
English It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA-sequencing demonstrated that the snoRNA host gene 16 (SNHG16) is significantly up-regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt-regulated transcription factors, including ASCL2, ETS2, and c-Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16 indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved in lipid metabolism was also observed in clinical tumors. Argonaute CrossLinking and ImmunoPrecipitation (AGO-CLIP) demonstrated that SNHG16 heavily binds AGO and has 27 AGO/miRNA target sites along its length, indicating that SNHG16 may act as a competing endogenous RNA (ceRNA) "sponging" miRNAs off their cognate targets. Most interestingly, half of the miRNA families with high confidence targets on SNHG16 also target the 3'UTR of Stearoyl-CoA Desaturase (SCD). SCD is involved in lipid metabolism and is down-regulated upon SNHG16 silencing. In conclusion, up-regulation of SNHG16 is a frequent event in CRC, likely caused by deregulated Wnt signaling. In vitro analyses demonstrate that SNHG16 may play an oncogenic role in CRC and that it affects genes involved in lipid metabolism, possible through ceRNA related mechanisms.
Language
  • English
Open access status
hybrid
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Persistent URL
https://folia.unifr.ch/global/documents/138142
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