Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes. View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Dries Rombaut, Hua-Sheng Chiu, Bieke Decaesteker, Celine Everaert, Nurten Yigit, Agathe Peltier, Isabelle Janoueix, Christoph Bartenhagen, Matthias Fischer, Stephen Roberts, Nicky D'Haene, Katleen De Preter, Frank Speleman, Geertrui Denecker, Pavel Sumazin, Jo Vandesompele, Steve Lefever, Pieter Mestdagh

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. More... »

PAGES

5685

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-42107-y

    DOI

    http://dx.doi.org/10.1038/s41598-019-42107-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113261550

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30952905


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