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Article: JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma

TitleJMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma
Authors
Keywordsanimal experiment
animal model
apoptosis
binding site
cancer prognosis
Issue Date2019
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2019, v. 10 n. 1, p. article no. 3319 How to Cite?
AbstractChromosome 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.
Persistent Identifierhttp://hdl.handle.net/10722/280342
ISSN
2019 Impact Factor: 12.121
2015 SCImago Journal Rankings: 6.539
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWong, M-
dc.contributor.authorSun, Y-
dc.contributor.authorXi, Z-
dc.contributor.authorMilazzo, G-
dc.contributor.authorPoulos, RC-
dc.contributor.authorBartenhagen, C-
dc.contributor.authorBell, JL-
dc.contributor.authorMayoh, C-
dc.contributor.authorHo, N-
dc.contributor.authorTee, AE-
dc.contributor.authorChen, X-
dc.contributor.authorLi, Y-
dc.contributor.authorCiaccio, R-
dc.contributor.authorLiu, PY-
dc.contributor.authorJiang, CC-
dc.contributor.authorLan, Q-
dc.contributor.author.Jayatilleke, N-
dc.contributor.authorCheung, BB-
dc.contributor.authorHaber, M-
dc.contributor.authorNorris, MD-
dc.contributor.authorZhang, XD-
dc.contributor.authorMarshall, GM-
dc.contributor.authorWang, JY-
dc.contributor.authorHüttelmaier, S-
dc.contributor.authorFischer, M-
dc.contributor.authorWong, JWH-
dc.contributor.authorXu, H-
dc.contributor.authorPerini, G-
dc.contributor.authorDong, Q-
dc.contributor.authorGeorge, RE-
dc.contributor.authorLiu, T-
dc.date.accessioned2020-02-07T07:39:45Z-
dc.date.available2020-02-07T07:39:45Z-
dc.date.issued2019-
dc.identifier.citationNature Communications, 2019, v. 10 n. 1, p. article no. 3319-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/280342-
dc.description.abstractChromosome 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.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectapoptosis-
dc.subjectbinding site-
dc.subjectcancer prognosis-
dc.titleJMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma-
dc.typeArticle-
dc.identifier.emailWong, JWH: jwhwong@hku.hk-
dc.identifier.authorityWong, JWH=rp02363-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-019-11132-w-
dc.identifier.pmid31346162-
dc.identifier.pmcidPMC6658504-
dc.identifier.scopuseid_2-s2.0-85070587006-
dc.identifier.hkuros309107-
dc.identifier.volume10-
dc.identifier.issue1-
dc.identifier.spagearticle no. 3319-
dc.identifier.epagearticle no. 3319-
dc.publisher.placeUnited Kingdom-
dc.identifier.f1000736274349-

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