Rombautd, Dries, Chiu, Hua-Sheng ORCID: 0000-0002-0296-5653, Decaesteker, Bieke, Everaert, Celine ORCID: 0000-0001-7772-4259, Yigit, Nurten, Peltier, Agathe, Janoueix, Isabelle, Bartenhagen, Christoph, Fischer, Matthias, Roberts, Stephen, D'Haene, Nicky, De Preter, Katleen, Speleman, Frank, Denecker, Geertrui, Sumazin, Pavel ORCID: 0000-0002-1215-4977, Vandesompele, Jo, Lefever, Steve and Mestdagh, Pieter (2019). Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rombautd, DriesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chiu, Hua-ShengUNSPECIFIEDorcid.org/0000-0002-0296-5653UNSPECIFIED
Decaesteker, BiekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Everaert, CelineUNSPECIFIEDorcid.org/0000-0001-7772-4259UNSPECIFIED
Yigit, NurtenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peltier, AgatheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janoueix, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenhagen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roberts, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
D'Haene, NickyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Preter, KatleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speleman, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denecker, GeertruiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sumazin, PavelUNSPECIFIEDorcid.org/0000-0002-1215-4977UNSPECIFIED
Vandesompele, JoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lefever, SteveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mestdagh, PieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-150967
DOI: 10.1038/s41598-019-42107-y
Journal or Publication Title: Sci Rep
Volume: 9
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LONG NONCODING RNAS; EXPRESSION; LNCRNA; PROLIFERATION; MECHANISMS; MUTATIONS; LANDSCAPE; AMPLIFICATION; TRANSCRIPTION; CONTRIBUTESMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15096

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