Regulation of Nuclear Hormone Receptors by MYCN-Driven miRNAs Impacts Neural Differentiation and Survival in Neuroblastoma Patients | Zendy

Diogo Ribeiro | Zendy; Marcus D. R. Klarqvist | Zendy; Ulrica Westermark | Zendy; Ganna Oliynyk | Zendy; Johanna Dzieran | Zendy; Anna Kock | Zendy; Carolina Savatier Banares | Zendy; Falk Hertwig | Zendy; John Inge Johnsen | Zendy; Matthias Fischer | Zendy; Per Kogner | Zendy; Jakob Lovén | Zendy; Marie ArsenianHenriksson | Zendy

Open Access

Regulation of Nuclear Hormone Receptors by MYCN-Driven miRNAs Impacts Neural Differentiation and Survival in Neuroblastoma Patients

Author(s) -

Diogo Ribeiro,

Marcus D. R. Klarqvist,

Ulrica Westermark,

Ganna Oliynyk,

Johanna Dzieran,

Anna Kock,

Carolina Savatier Banares,

Falk Hertwig,

John Inge Johnsen,

Matthias Fischer,

Per Kogner,

Jakob Lovén,

Marie ArsenianHenriksson

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.06.052

Subject(s) - neuroblastoma , nuclear receptor , cancer research , biology , microrna , glucocorticoid receptor , estrogen receptor , n myc , receptor , phenotype , signal transduction , bioinformatics , medicine , endocrinology , transcription factor , cancer , microbiology and biotechnology , genetics , gene , breast cancer , ganglioneuroma , cell culture

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∼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 unique NHR signature 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∼92-regulated NHRs in neuroblastoma biology, thereby providing a potential differentiation approach for treating neuroblastoma patients.

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