Wong, Matthew ORCID: 0000-0003-2680-961X, Sun, Yuting, Xi, Zhichao, Milazzo, Giorgio ORCID: 0000-0002-1930-4763, Poulos, Rebecca C., Bartenhagen, Christoph, Bell, Jessica L., Mayoh, Chelsea, Ho, Nicholas, Tee, Andrew E., Chen, Xiaoqiong, Li, Yang, Ciaccio, Roberto ORCID: 0000-0003-3024-9205, Liu, Pei Y., Jiang, Chen C., Lan, Qing, Jayatilleke, Nisitha, Cheung, Belamy B., Haber, Michelle ORCID: 0000-0003-2036-8817, Norris, Murray D., Zhang, Xu D., Marshall, Glenn M., Wang, Jenny Y., Huettelmaier, Stefan, Fischer, Matthias, Wong, Jason W. H., Xu, Hongxi, Perini, Giovanni, Dong, Qihan, George, Rani E. and Liu, Tao ORCID: 0000-0001-6244-7316 (2019). JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wong, MatthewUNSPECIFIEDorcid.org/0000-0003-2680-961XUNSPECIFIED
Sun, YutingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xi, ZhichaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milazzo, GiorgioUNSPECIFIEDorcid.org/0000-0002-1930-4763UNSPECIFIED
Poulos, Rebecca C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenhagen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bell, Jessica L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayoh, ChelseaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ho, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tee, Andrew E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, XiaoqiongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, YangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciaccio, RobertoUNSPECIFIEDorcid.org/0000-0003-3024-9205UNSPECIFIED
Liu, Pei Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, Chen C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lan, QingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jayatilleke, NisithaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheung, Belamy B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haber, MichelleUNSPECIFIEDorcid.org/0000-0003-2036-8817UNSPECIFIED
Norris, Murray D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, Xu D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marshall, Glenn M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, Jenny Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huettelmaier, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wong, Jason W. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, HongxiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perini, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dong, QihanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, Rani E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, TaoUNSPECIFIEDorcid.org/0000-0001-6244-7316UNSPECIFIED
URN: urn:nbn:de:hbz:38-134715
DOI: 10.1038/s41467-019-11132-w
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
READ ALIGNMENT; GENE; EXPRESSION; TRANSCRIPTION; DISCOVERY; CANCER; GAIN; DEPENDENCIES; INHIBITION; ONCOGENESMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13471

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