- Title
- JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma
- Creator
- Wong, Matthew; Sun, Yuting; Xi, Zhichao; Milazzo, Giorgio; Poulos, Rebecca C.; Bartenhagen, Christoph; Bell, Jessica L.; Mayoh, Chelsea; Ho, Nicholas; Tee, Andrew E.; Chen, Xiaoqiong; Li, Yang; Ciaccio, Roberto; Liu, Pei Y.; Jiang, Chen C.; Lan, Qing; Jayatilleke, Nisitha; Cheung, Belamy B.; Haber, Michelle; Norris, Murray D.; Zhang, Xu D.; Marshall, GM; Wang, JY; Huettelmaier, S; Fischer, M; Wong, JWH; Xu, H; Perini, G; Dong, Q; George, RE; Liu, T
- Relation
- Nature Communications Vol. 10, Issue 1, no. 3319
- Publisher Link
- http://dx.doi.org/10.1038/s41467-019-11132-w
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- gene; JMJD6; neuroblastoma; in vitro; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1455257
- Identifier
- uon:45069
- Identifier
- ISSN:2041-1723
- Rights
- © Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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