Universität zu Köln

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

Full text not available from this repository.

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:	Creators Email ORCID ORCID Put Code Rombautd, Dries UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiu, Hua-Sheng UNSPECIFIED orcid.org/0000-0002-0296-5653 UNSPECIFIED Decaesteker, Bieke UNSPECIFIED UNSPECIFIED UNSPECIFIED Everaert, Celine UNSPECIFIED orcid.org/0000-0001-7772-4259 UNSPECIFIED Yigit, Nurten UNSPECIFIED UNSPECIFIED UNSPECIFIED Peltier, Agathe UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoueix, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartenhagen, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Roberts, Stephen UNSPECIFIED UNSPECIFIED UNSPECIFIED D'Haene, Nicky UNSPECIFIED UNSPECIFIED UNSPECIFIED De Preter, Katleen UNSPECIFIED UNSPECIFIED UNSPECIFIED Speleman, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Denecker, Geertrui UNSPECIFIED UNSPECIFIED UNSPECIFIED Sumazin, Pavel UNSPECIFIED orcid.org/0000-0002-1215-4977 UNSPECIFIED Vandesompele, Jo UNSPECIFIED UNSPECIFIED UNSPECIFIED Lefever, Steve UNSPECIFIED UNSPECIFIED UNSPECIFIED Mestdagh, Pieter UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language LONG NONCODING RNAS; EXPRESSION; LNCRNA; PROLIFERATION; MECHANISMS; MUTATIONS; LANDSCAPE; AMPLIFICATION; TRANSCRIPTION; CONTRIBUTES Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15096