Ribeiro, Diogo ORCID: 0000-0003-4400-8752, Klarqvist, Marcus D. R. ORCID: 0000-0001-7630-2708, Westermark, Ulrica K., Oliynyk, Ganna, Dzieran, Johanna, Kock, Anna, Banares, Carolina Savatier, Hertwig, Falk ORCID: 0000-0003-4784-6516, Johnsen, John Inge, Fischer, Matthias, Kogner, Per ORCID: 0000-0002-2202-9694, Loven, Jakob and Henriksson, Marie Arsenian (2016). Regulation of Nuclear Hormone Receptors by MYCN-Driven miRNAs Impacts Neural Differentiation and Survival in Neuroblastoma Patients. Cell Reports, 16 (4). S. 979 - 994. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

MYCN amplification and MYC signaling are associated with high-risk neuroblastoma with poor prognosis. Treating these tumors remains challenging, although therapeutic approaches stimulating differentiation have generated considerable interest. We have previously shown that the MYCN-regulated miR-17 similar to 92 cluster inhibits neuroblastoma differentiation by repressing estrogen receptor alpha. Here, we demonstrate that this microRNA (miRNA) cluster selectively targets several members of the nuclear hormone receptor (NHR) superfamily, and we present a uniqueNHRsignature associated with the survival of neuroblastoma patients. We found that suppressing glucocorticoid receptor (GR) expression in MYCN-driven patient and mouse tumors was associated with an undifferentiated phenotype and decreased survival. Importantly, MYCN inhibition and subsequent reactivation of GR signaling promotes neural differentiation and reduces tumor burden. Our findings reveal a key role for the miR-17 similar to 92-regulated NHRs in neuroblastoma biology, thereby providing a potential differentiation approach for treating neuroblastoma patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ribeiro, DiogoUNSPECIFIEDorcid.org/0000-0003-4400-8752UNSPECIFIED
Klarqvist, Marcus D. R.UNSPECIFIEDorcid.org/0000-0001-7630-2708UNSPECIFIED
Westermark, Ulrica K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliynyk, GannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dzieran, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kock, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Banares, Carolina SavatierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hertwig, FalkUNSPECIFIEDorcid.org/0000-0003-4784-6516UNSPECIFIED
Johnsen, John IngeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kogner, PerUNSPECIFIEDorcid.org/0000-0002-2202-9694UNSPECIFIED
Loven, JakobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henriksson, Marie ArsenianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-269565
DOI: 10.1016/j.celrep.2016.06.052
Journal or Publication Title: Cell Reports
Volume: 16
Number: 4
Page Range: S. 979 - 994
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; NEURONAL DIFFERENTIATION; N-MYC; SECRETOGRANIN-II; SPONTANEOUS REGRESSION; MESSENGER-RNA; IN-VIVO; EXPRESSION; MICRORNASMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26956

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