Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes
| Autor: | Pavel Sumazin, Nurten Yigit, Stephen S. Roberts, Pieter Mestdagh, Hua-Sheng Chiu, Matthias Fischer, Jo Vandesompele, Geertrui Denecker, Nicky D'Haene, Katleen De Preter, Isabelle Janoueix-Lerosey, Frank Speleman, Steve Lefever, Christoph Bartenhagen, Bieke Decaesteker, Dries Rombaut, Agathe Peltier, Celine Everaert |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
EXPRESSION Stromal cell lcsh:Medicine Computational biology Biology LONG NONCODING RNAS Article MECHANISMS CONTRIBUTES 03 medical and health sciences 0302 clinical medicine Neuroblast Transcription (biology) Phénomènes atmosphériques Neuroblastoma Gene expression medicine Medicine and Health Sciences TRANSCRIPTION lcsh:Science Gene neoplasms LNCRNA MEG3 Multidisciplinary LANDSCAPE MUTATIONS lcsh:R PROLIFERATION Biology and Life Sciences AMPLIFICATION medicine.disease 030104 developmental biology lcsh:Q Signal transduction 030217 neurology & neurosurgery |
| Zdroj: | SCIENTIFIC REPORTS Scientific Reports Scientific reports, 9 (1 Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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