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

Christensen, Lise Lotte; True, Kirsten; Hamilton, Mark; Nielsen, Morten Muhlig; Damas, Nkerorema Djodji; Damgaard, Christian Kroun; Ongen, Halit; Dermitzakis, Emmanouil T.; Bramsen, Jesper B.; Pedersen, Jakob Skou; Lund, Anders H.; Vang, Søren; Stribolt, Katrine; Madsen, Mogens Rørbæk; Laurberg, Søren; McGuire, Sean E.; Ørntoft, Torben F.; Andersen, Claus Lindbjerg

doi:10.1016/j.molonc.2016.06.003

Cited by 160 publications

(172 citation statements)

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“…For example, SNHG16 has been found to be up-regulated in colorectal cancers and affected the genes involved in lipid metabolism [15]. In a recent study, SNHG16 has been found to be overexpressed and contributed to the development of non-small cell lung cancer (NSCLC) via inhibition of miR-146a [16].…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

Cai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. Methods: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. Results: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. Conclusion: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.

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Section: Discussionmentioning

confidence: 99%

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

Cai

et al. 2018

Cell Physiol Biochem

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“…57. The Anoikis resistance assay was performed with Corning Costar Ultra-Low attachment 24-well plates (Corning Life Science, Tewksbury, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer

Seitz

Christensen

et al. 2017

Sci Rep

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108

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Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were significantly dys-regulated in BC. Five lncRNAs; LINC00958, LINC01296, LINC00355, LNC-CMC1-1 and LNC-ALX1-2 were selected for further analyses. Silencing of LINC00958 or LINC01296 in vitro reduced both cell viability and migration. Knock-down of LINC00958 also affected invasion and resistance to anoikis. These cellular effects could be linked to direct/indirect regulation of protein coding mRNAs involved in cell death/survival, proliferation and cellular movement. Finally, we showed that LINC00958 binds proteins involved in regulation and initiation of translation and in post-transcriptional modification of RNA, including Metadherin, which has previously been associated with BC. Our analyses identified novel lncRNAs in BC that likely act as oncogenic drivers contributing to an aggressive cancerous phenotype likely through interaction with proteins involved in initiation of translation and/or post-transcriptional modification of RNA.

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“…Probably, the colorectal cancer cases contain mutated versions of XPOT that might lead to transfer of oncoproteins and ETC-1922159 might act as an inhibitor for mutated XPOT. SNHG16 (snoRNA host gene 16) has been demonstrated to be significantly up regulated in adenomas and all stages of CRC 206 . Christensen et al 206 report positive correlation with Wnt regulated factors like ASCL2 which is known for contributing to stemness.…”

Section: Dicationmentioning

confidence: 99%

“…SNHG16 (snoRNA host gene 16) has been demonstrated to be significantly up regulated in adenomas and all stages of CRC 206 . Christensen et al 206 report positive correlation with Wnt regulated factors like ASCL2 which is known for contributing to stemness. Also, silencing of SNHG16 has been found to affect lipid metabolism and increase apoptotic cell death.…”

Section: Dicationmentioning

confidence: 99%

“…Probably, the colorectal cancer cases contain mutated versions of XPOT that might lead to transfer of oncoproteins and ETC-1922159 might act as an inhibitor for mutated XPOT. 206 report positive correlation with Wnt regulated factors like ASCL2 which is known for contributing to stemness. Also, silencing of SNHG16 has been found to affect lipid metabolism and increase apoptotic cell death.…”

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confidence: 92%

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Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

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WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stemness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2 nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1 , we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2 nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3 rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3 rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest. KEYWORDS -WNT pathway; porcupine inhibitor ETC-1922159; sensitivity analysis; colorectal cancer; unknown biological hypotheses; combinatorial search space; support vector ranking Conference, from 6-11 August 2017, held Significance WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. Often, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be involved in the pathway. The current work reveals at in silico level, the 3rd order WNT10B associated combinations that might be affected by the admin...

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

Cited by 160 publications

References 67 publications

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma

Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

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