Advanced search
1 file | 7.28 MB Add to list

Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes

Author
Organization
Abstract
Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblastoma cell lines and various cellular perturbation model systems to define the neuroblastoma lincRNome and map lincRNAs up- and downstream of neuroblastoma driver genes MYCN, ALK and PHOX2B. Each of these driver genes controls the expression of a particular subset of lincRNAs, several of which are associated with poor survival and are differentially expressed in neuroblastoma tumors compared to neuroblasts. By integrating RNA sequencing data from both primary tumor tissue and cancer cell lines, we demonstrate that several of these lincRNAs are expressed in stromal cells. Deconvolution of primary tumor gene expression data revealed a strong association between stromal cell composition and driver gene status, resulting in differential expression of these lincRNAs. We also explored lincRNAs that putatively act upstream of neuroblastoma driver genes, either as presumed modulators of driver gene activity, or as modulators of effectors regulating driver gene expression. This analysis revealed strong associations between the neuroblastoma lincRNAs MIAT and MEG3 and MYCN and PHOX2B activity or expression. Together, our results provide a comprehensive catalogue of the neuroblastoma lincRNome, highlighting lincRNAs up- and downstream of key neuroblastoma driver genes. This catalogue forms a solid basis for further functional validation of candidate neuroblastoma lincRNAs.
Keywords
LONG NONCODING RNAS, EXPRESSION, LNCRNA, PROLIFERATION, MECHANISMS, MUTATIONS, LANDSCAPE, AMPLIFICATION, TRANSCRIPTION, CONTRIBUTES

Downloads

  • s41598-019-42107-y.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 7.28 MB

Citation

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

MLA
Rombaut, Dries, et al. “Integrative Analysis Identifies LincRNAs Up- and Downstream of Neuroblastoma Driver Genes.” SCIENTIFIC REPORTS, vol. 9, 2019.
APA
Rombaut, D., Chiu, H.-S., Decaesteker, B., Everaert, C., Yigit, N., Pelthier, A., … Mestdagh, P. (2019). Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes. SCIENTIFIC REPORTS, 9.
Chicago author-date
Rombaut, Dries, Hua-Sheng Chiu, Bieke Decaesteker, Celine Everaert, Nurten Yigit, Agathe Pelthier, Isabelle Janoueix, et al. 2019. “Integrative Analysis Identifies LincRNAs Up- and Downstream of Neuroblastoma Driver Genes.” SCIENTIFIC REPORTS 9.
Chicago author-date (all authors)
Rombaut, Dries, Hua-Sheng Chiu, Bieke Decaesteker, Celine Everaert, Nurten Yigit, Agathe Pelthier, Isabelle Janoueix, Christophe Bartenhagen, Matthias Fischer, Stephen Roberts, Nicky D’Haene, Katleen De Preter, Franki Speleman, Geertrui Denecker, Pavel Sumazin, Jo Vandesompele, Steve Lefever, and Pieter Mestdagh. 2019. “Integrative Analysis Identifies LincRNAs Up- and Downstream of Neuroblastoma Driver Genes.” SCIENTIFIC REPORTS 9.
Vancouver
1.
Rombaut D, Chiu H-S, Decaesteker B, Everaert C, Yigit N, Pelthier A, et al. Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes. SCIENTIFIC REPORTS. 2019;9.
IEEE
[1]
D. Rombaut et al., “Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes,” SCIENTIFIC REPORTS, vol. 9, 2019.
@article{8608832,
  abstract     = {Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblastoma cell lines and various cellular perturbation model systems to define the neuroblastoma lincRNome and map lincRNAs up- and downstream of neuroblastoma driver genes MYCN, ALK and PHOX2B. Each of these driver genes controls the expression of a particular subset of lincRNAs, several of which are associated with poor survival and are differentially expressed in neuroblastoma tumors compared to neuroblasts. By integrating RNA sequencing data from both primary tumor tissue and cancer cell lines, we demonstrate that several of these lincRNAs are expressed in stromal cells. Deconvolution of primary tumor gene expression data revealed a strong association between stromal cell composition and driver gene status, resulting in differential expression of these lincRNAs. We also explored lincRNAs that putatively act upstream of neuroblastoma driver genes, either as presumed modulators of driver gene activity, or as modulators of effectors regulating driver gene expression. This analysis revealed strong associations between the neuroblastoma lincRNAs MIAT and MEG3 and MYCN and PHOX2B activity or expression. Together, our results provide a comprehensive catalogue of the neuroblastoma lincRNome, highlighting lincRNAs up- and downstream of key neuroblastoma driver genes. This catalogue forms a solid basis for further functional validation of candidate neuroblastoma lincRNAs.},
  articleno    = {5685},
  author       = {Rombaut, Dries and Chiu, Hua-Sheng and Decaesteker, Bieke and Everaert, Celine and Yigit, Nurten and Pelthier, Agathe and Janoueix, Isabelle and Bartenhagen, Christophe and Fischer, Matthias and Roberts, Stephen and D'Haene, Nicky and De Preter, Katleen and Speleman, Franki and Denecker, Geertrui and Sumazin, Pavel and Vandesompele, Jo and Lefever, Steve and Mestdagh, Pieter},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {LONG NONCODING RNAS,EXPRESSION,LNCRNA,PROLIFERATION,MECHANISMS,MUTATIONS,LANDSCAPE,AMPLIFICATION,TRANSCRIPTION,CONTRIBUTES},
  language     = {eng},
  pages        = {13},
  title        = {Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes},
  url          = {http://dx.doi.org/10.1038/s41598-019-42107-y},
  volume       = {9},
  year         = {2019},
}

Altmetric
View in Altmetric
Web of Science
Times cited: