Advanced search
Add to list

Long noncoding RNA SILC1 is an upstream regulator of SOX11 in neuroblastoma

(2020)
Author
Organization
Abstract
Neuroblastoma (NB) is the most common extra cranial solid tumor during early childhood, arising from progenitors of the sympathetic nervous system. We identified the adrenergic specific transcription factor SOX11 as a lineage dependency factor and a putative master regulator of epigenetic plasticity in NB. Using ChIP-seq we mapped the sites of SOX11 DNA binding and identified several genes encoding components of major epigenetic regulatory protein complexes. In order to gain more insight into the long-range control of SOX11 expression in NB cells, we analyzed H3K27ac data to map noncoding regulatory enhancer regions. We identified a super-enhancer in a large protein coding gene poor region 1.1 Mb distal to the SOX11 locus. This region coincides with the previously annotated lncRNA coined SILC1 which was shown to be implicated in neurite outgrowth and neuron regeneration. SILC1 was found to be strongly expressed in adrenergic NB cells and highly correlated to SOX11 expression levels in both NB cell lines and tumors. Also, in the normal developing sympathetic lineage and across a wide panel of cancer cell line entities and adrenergic/mesenchymal isogenic cell line pairs, the SILC1 expression pattern closely resembled that of SOX11. To investigate the chromatin conformation of the SOX11 neighbouring (super-)enhancers, we performed 4C-seq analysis and observed looping in this highly active region between the SOX11 and SILC1 promoter in adrenergic NB cells while absent in the mesenchymal NB cell line SH-EP. We are currently unraveling the role of SILC1 using ChIRP sequencing and a dCas9-KRAB silencing system. In conclusion, our data suggests that SILC1 plays a crucial role in controlling SOX11 expression levels thus offering an entry point for targeted therapy for SOX11-driven neuroblastoma.

Citation

Please use this url to cite or link to this publication:

MLA
Louwagie, Amber, et al. Long Noncoding RNA SILC1 Is an Upstream Regulator of SOX11 in Neuroblastoma. 2020.
APA
Louwagie, A., Decaesteker, B., D’haene, E., Delhaye, L., de Bony de Lavergne, E., Van Neste, C., … Speleman, F. (2020). Long noncoding RNA SILC1 is an upstream regulator of SOX11 in neuroblastoma. Presented at the Keystone:  Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities, Keystone Resort, Keystone, CO, USA.
Chicago author-date
Louwagie, Amber, Bieke Decaesteker, Eva D’haene, Louis Delhaye, Eric de Bony de Lavergne, Christophe Van Neste, Rogier Versteeg, et al. 2020. “Long Noncoding RNA SILC1 Is an Upstream Regulator of SOX11 in Neuroblastoma.” In .
Chicago author-date (all authors)
Louwagie, Amber, Bieke Decaesteker, Eva D’haene, Louis Delhaye, Eric de Bony de Lavergne, Christophe Van Neste, Rogier Versteeg, Sara Ek, Björn Menten, Jan Koster, Johan van Nes, Sven Eyckerman, Pieter Mestdagh, Katleen De Preter, and Franki Speleman. 2020. “Long Noncoding RNA SILC1 Is an Upstream Regulator of SOX11 in Neuroblastoma.” In .
Vancouver
1.
Louwagie A, Decaesteker B, D’haene E, Delhaye L, de Bony de Lavergne E, Van Neste C, et al. Long noncoding RNA SILC1 is an upstream regulator of SOX11 in neuroblastoma. In 2020.
IEEE
[1]
A. Louwagie et al., “Long noncoding RNA SILC1 is an upstream regulator of SOX11 in neuroblastoma,” presented at the Keystone:  Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities, Keystone Resort, Keystone, CO, USA, 2020.
@inproceedings{8642338,
  abstract     = {Neuroblastoma (NB) is the most common extra cranial solid tumor during early childhood, arising from progenitors of the sympathetic nervous system. We identified the adrenergic specific transcription factor SOX11 as a lineage dependency factor and a putative master regulator of epigenetic plasticity in NB. Using ChIP-seq we mapped the sites of SOX11 DNA binding and identified several genes encoding components of major epigenetic regulatory protein complexes. In order to gain more insight into the long-range control of SOX11 expression in NB cells, we analyzed H3K27ac data to map noncoding regulatory enhancer regions. We identified a super-enhancer in a large protein coding gene poor region 1.1 Mb distal to the SOX11 locus. This region coincides with the previously annotated lncRNA coined SILC1 which was shown to be implicated in neurite outgrowth and neuron regeneration. SILC1 was found to be strongly expressed in adrenergic NB cells and highly correlated to SOX11 expression levels in both NB cell lines and tumors. Also, in the normal developing sympathetic lineage and across a wide panel of cancer cell line entities and adrenergic/mesenchymal isogenic cell line pairs, the SILC1 expression pattern closely resembled that of SOX11. To investigate the chromatin conformation of the SOX11 neighbouring (super-)enhancers, we performed 4C-seq analysis and observed looping in this highly active region between the SOX11 and SILC1 promoter in adrenergic NB cells while absent in the mesenchymal NB cell line SH-EP. We are currently unraveling the role of SILC1 using ChIRP sequencing and a dCas9-KRAB silencing system. In conclusion, our data suggests that SILC1 plays a crucial role in controlling SOX11 expression levels thus offering an entry point for targeted therapy for SOX11-driven neuroblastoma. 
},
  author       = {Louwagie, Amber and Decaesteker, Bieke and D'haene, Eva and Delhaye, Louis and de Bony de Lavergne, Eric and Van Neste, Christophe and Versteeg, Rogier and Ek, Sara and Menten, Björn and Koster, Jan and van Nes, Johan and Eyckerman, Sven and Mestdagh, Pieter and De Preter, Katleen and Speleman, Franki},
  location     = {Keystone Resort, Keystone, CO, USA},
  title        = {Long noncoding RNA SILC1 is an upstream regulator of SOX11 in neuroblastoma},
  year         = {2020},
}