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JMJD6 Is a Tumorigenic Factor and Therapeutic Target in Neuroblastoma

JMJD6 Is a Tumorigenic Factor and Therapeutic Target in Neuroblastoma

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, etc.

Nat Commun. 2019 Jul 25;10(1):3319.

PMID: 31346162

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416065	JMJD6 human			Price

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