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

Lise-Lotte Christensen; Kirsten Kallesøe True; M.P. Hamilton; Morten Muhlig Nielsen; Nkerorema Djodji Damas; Christian Kroun Damgaard; Halit Ongen; Emmanouil T Dermitzakis; Jesper Bramsen; Jakob Skou Pedersen; Anders Henrik Lund; Søren Vang; Katrine Stribolt; Mogens Rørbæk Madsen; Søren Laurberg; Sean McGuire; Torben Falck Ørntoft; Claus Lindbjerg Andersen

doi:10.1016/j.molonc.2016.06.003

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

Lise-Lotte Christensen, Kirsten Kallesøe True, M.P. Hamilton, Morten Muhlig Nielsen, Nkerorema Djodji Damas, Christian Kroun Damgaard, Halit Ongen, Emmanouil T Dermitzakis, Jesper Bramsen, Jakob Skou Pedersen, Anders Henrik Lund, Søren Vang, Katrine Stribolt, Mogens Rørbæk Madsen, Søren Laurberg, Sean McGuire, Torben Falck Ørntoft, Claus Lindbjerg Andersen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

162 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Molecular Oncology
Volume	10
Issue	8
Pages (from-to)	1266-1282
Number of pages	16
ISSN	1574-7891
DOIs	https://doi.org/10.1016/j.molonc.2016.06.003
Publication status	Published - Oct 2016

Keywords

AGO-CLIP
Colorectal cancer
Functional analyses
Long non-coding RNAs
SNHG16
Wnt pathway

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Christensen, L.-L., True, K. K., Hamilton, M. P., Nielsen, M. M., Djodji Damas, N., Damgaard, C. K., Ongen, H., Dermitzakis, E. T., Bramsen, J., Pedersen, J. S., Lund, A. H., Vang, S., Stribolt, K., Madsen, M. R., Laurberg, S., McGuire, S., Ørntoft, T. F., & Andersen, C. L. (2016). SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism. Molecular Oncology, 10(8), 1266-1282. https://doi.org/10.1016/j.molonc.2016.06.003

@article{8ea66dc4cce140c29d0b65f51bdf6287,

title = "SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism",

abstract = "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.",

keywords = "AGO-CLIP, Colorectal cancer, Functional analyses, Long non-coding RNAs, SNHG16, Wnt pathway",

author = "Lise-Lotte Christensen and True, \{Kirsten Kalles{\o}e\} and M.P. Hamilton and Nielsen, \{Morten Muhlig\} and \{Djodji Damas\}, Nkerorema and Damgaard, \{Christian Kroun\} and Halit Ongen and Dermitzakis, \{Emmanouil T\} and Jesper Bramsen and Pedersen, \{Jakob Skou\} and Lund, \{Anders Henrik\} and S{\o}ren Vang and Katrine Stribolt and Madsen, \{Mogens R{\o}rb{\ae}k\} and S{\o}ren Laurberg and Sean McGuire and {\O}rntoft, \{Torben Falck\} and Andersen, \{Claus Lindbjerg\}",

year = "2016",

month = oct,

doi = "10.1016/j.molonc.2016.06.003",

language = "English",

volume = "10",

pages = "1266--1282",

journal = "Molecular Oncology",

issn = "1574-7891",

publisher = "John Wiley and Sons Ltd",

number = "8",

}

Christensen, L-L, True, KK, Hamilton, MP, Nielsen, MM, Djodji Damas, N, Damgaard, CK, Ongen, H, Dermitzakis, ET, Bramsen, J, Pedersen, JS, Lund, AH, Vang, S, Stribolt, K, Madsen, MR, Laurberg, S, McGuire, S, Ørntoft, TF & Andersen, CL 2016, 'SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism', Molecular Oncology, vol. 10, no. 8, pp. 1266-1282. https://doi.org/10.1016/j.molonc.2016.06.003

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism. / Christensen, Lise-Lotte; True, Kirsten Kallesøe; Hamilton, M.P. et al.
In: Molecular Oncology, Vol. 10, No. 8, 10.2016, p. 1266-1282.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

AU - Christensen, Lise-Lotte

AU - True, Kirsten Kallesøe

AU - Hamilton, M.P.

AU - Nielsen, Morten Muhlig

AU - Djodji Damas, Nkerorema

AU - Damgaard, Christian Kroun

AU - Ongen, Halit

AU - Dermitzakis, Emmanouil T

AU - Bramsen, Jesper

AU - Pedersen, Jakob Skou

AU - Lund, Anders Henrik

AU - Vang, Søren

AU - Stribolt, Katrine

AU - Madsen, Mogens Rørbæk

AU - Laurberg, Søren

AU - McGuire, Sean

AU - Ørntoft, Torben Falck

AU - Andersen, Claus Lindbjerg

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

KW - AGO-CLIP

KW - Colorectal cancer

KW - Functional analyses

KW - Long non-coding RNAs

KW - SNHG16

KW - Wnt pathway

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U2 - 10.1016/j.molonc.2016.06.003

DO - 10.1016/j.molonc.2016.06.003

M3 - Journal article

C2 - 27396952

SN - 1574-7891

VL - 10

SP - 1266

EP - 1282

JO - Molecular Oncology

JF - Molecular Oncology

IS - 8

ER -

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

Abstract

Keywords

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