JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-07-25

AUTHORS

Matthew Wong, Yuting Sun, Zhichao Xi, Giorgio Milazzo, Rebecca C. Poulos, Christoph Bartenhagen, Jessica L. Bell, Chelsea Mayoh, Nicholas Ho, Andrew E. Tee, Xiaoqiong Chen, Yang Li, Roberto Ciaccio, Pei Y. Liu, Chen C. Jiang, Qing Lan, Nisitha Jayatilleke, Belamy B. Cheung, Michelle Haber, Murray D. Norris, Xu D. Zhang, Glenn M. Marshall, Jenny Y. Wang, Stefan Hüttelmaier, Matthias Fischer, Jason W. H. Wong, Hongxi Xu, Giovanni Perini, Qihan Dong, Rani E. George, Tao Liu

ABSTRACT

Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy. More... »

PAGES

3319

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    10

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-11132-w

    DOI

    http://dx.doi.org/10.1038/s41467-019-11132-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1119795329

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31346162


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