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MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma

MYCN is a master regulator controlling many processes necessary for tumor cell survival. Here, we unravel a microRNA network that causes tumor suppressive effects in MYCN-amplified neuroblastoma cells. In profiling studies, histone deacetylase (HDAC) inhibitor treatment most strongly induced miR-183...

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Hauptverfasser: Lodrini, Marco (VerfasserIn) , Oehme, Ina (VerfasserIn) , Schröder, Christina (VerfasserIn) , Milde, Till (VerfasserIn) , Schier, Marie Catherine (VerfasserIn) , Kopp-Schneider, Annette (VerfasserIn) , Schulte, Johannes H. (VerfasserIn) , Fischer, Matthias (VerfasserIn) , De Preter, Katleen (VerfasserIn) , Pattyn, Filip (VerfasserIn) , Castoldi, Mirco (VerfasserIn) , Muckenthaler, Martina (VerfasserIn) , Kulozik, Andreas (VerfasserIn) , Westermann, Frank (VerfasserIn) , Witt, Olaf (VerfasserIn) , Deubzer, Hedwig (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 26 April 2013
In: Nucleic acids research
Year: 2013, Jahrgang: 41, Heft: 12, Pages: 6018-6033
ISSN:1362-4962
DOI:10.1093/nar/gkt346
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/nar/gkt346
Volltext
Verfasserangaben:Marco Lodrini, Ina Oehme, Christina Schroeder, Till Milde, Marie C. Schier, Annette Kopp-Schneider, Johannes H. Schulte, Matthias Fischer, Katleen De Preter, Filip Pattyn, Mirco Castoldi, Martina U. Muckenthaler, Andreas E. Kulozik, Frank Westermann, Olaf Witt and Hedwig E. Deubzer
Beschreibung
Zusammenfassung:MYCN is a master regulator controlling many processes necessary for tumor cell survival. Here, we unravel a microRNA network that causes tumor suppressive effects in MYCN-amplified neuroblastoma cells. In profiling studies, histone deacetylase (HDAC) inhibitor treatment most strongly induced miR-183. Enforced miR-183 expression triggered apoptosis, and inhibited anchorage-independent colony formation in vitro and xenograft growth in mice. Furthermore, the mechanism of miR-183 induction was found to contribute to the cell death phenotype induced by HDAC inhibitors. Experiments to identify the HDAC(s) involved in miR-183 transcriptional regulation showed that HDAC2 depletion induced miR-183. HDAC2 overexpression reduced miR-183 levels and counteracted the induction caused by HDAC2 depletion or HDAC inhibitor treatment. MYCN was found to recruit HDAC2 in the same complexes to the miR-183 promoter, and HDAC2 depletion enhanced promoter-associated histone H4 pan-acetylation, suggesting epigenetic changes preceded transcriptional activation. These data reveal miR-183 tumor suppressive properties in neuroblastoma that are jointly repressed by MYCN and HDAC2, and suggest a novel way to bypass MYCN function.
Beschreibung:Gesehen am 19.05.2021
Beschreibung:Online Resource
ISSN:1362-4962
DOI:10.1093/nar/gkt346

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