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Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox

Yang, J; Milasta, S; Hu, D; AlTahan, AM; Interiano, RB; Zhou, J; Davidson, J; ... Davidoff, AM; + view all (2017) Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox. Cancer Research , 77 (17) pp. 4626-4638. 10.1158/0008-5472.CAN-16-0826. Green open access

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Abstract

Histone lysine demethylases facilitate the activity of oncogenic transcription factors, including possibly MYC. Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells, where MYC is often overexpressed. We also identified the approved small-molecule antifungal agent ciclopirox as a novel pan-histone demethylase inhibitor. Ciclopirox targeted several histone demethylases, including KDM4B implicated in MYC function. Accordingly, ciclopirox inhibited Myc signaling in parallel with mitochondrial oxidative phosphorylation, resulting in suppression of neuroblastoma cell viability and inhibition of tumor growth associated with an induction of differentiation. Our findings provide new insights into epigenetic regulation of MYC function and suggest a novel pharmacologic basis to target histone demethylases as an indirect MYC-targeting approach for cancer therapy.

Type: Article
Title: Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/0008-5472.CAN-16-0826
Publisher version: http://dx.doi.org/10.1158/0008-5472.CAN-16-0826
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Histone demethylase, Neuroblastoma, Ciclopirox
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10055862
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