Evidence map›Paper›PMID 27081402›Full record

ArticleClinical epigenetics2016

The epigenetic modifier JMJD6 is amplified in mammary tumors and cooperates with c-Myc to enhance cellular transformation, tumor progression, and metastasis.

Olga Aprelikova, Kenny Chen, Lara H El Touny, Constance Brignatz-Guittard, Justin Han, Tinghu Qiu, Howard H Yang, Maxwell P Lee, Min Zhu, Jeffrey E Green

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
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  4. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
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  10. JMJD family proteins in cancer and inflammation.Signal transduction and targeted therapy · 2022
    Review
  11. A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Article
  13. Roles of enhancer RNAs in sex hormone-dependent cancers.Journal of cancer research and clinical oncology · 2022
    Review
  14. Article
  15. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Olga AprelikovaLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Kenny ChenLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Lara H El TounyLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Constance Brignatz-GuittardLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Justin HanLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Tinghu QiuLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Howard H YangLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Maxwell P LeeLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Min ZhuLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
Jeffrey E GreenLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 4054, 37 Convent Dr., Bethesda, MD 20892 USA.
National Institutes of Health · USNational Cancer Institute · US

Funding

Intramural NIH HHS
6 · The paper itself

Abstract

backgroundOncogene overexpression in primary cells often triggers the induction of a cellular safeguard response promoting senescence or apoptosis. Secondary cooperating genetic events are generally required for oncogene-induced tumorigenesis to overcome these biologic obstacles. We employed comparative genomic hybridization for eight genetically engineered mouse models of mammary cancer to identify loci that might harbor genes that enhance oncogene-induced tumorigenesis.

resultsUnlike many other mammary tumor models, the MMTV-Myc tumors displayed few copy number variants except for amplification of distal mouse chromosome 11 in 80 % of the tumors (syntenic to human 17q23-qter often amplified in human breast cancer). Analyses of candidate genes located in this region identified JMJD6 as an epigenetic regulatory gene that cooperates with Myc to enhance tumorigenesis. It suppresses Myc-induced apoptosis under varying stress conditions through inhibition of p19ARF messenger RNA (mRNA) and protein, leading to reduced levels of p53. JMJD6 binds to the p19ARF promoter and exerts its inhibitory function through demethylation of H4R3me2a. JMJD6 overexpression in MMTV-Myc cell lines increases tumor burden, induces EMT, and greatly enhances tumor metastasis. Importantly, we demonstrate that co-expression of high levels of JMJD6 and Myc is associated with poor prognosis for human ER+ breast cancer patients.

conclusionsA novel epigenetic mechanism has been identified for how JMJD6 cooperates with Myc during oncogenic transformation. Combined high expression of Myc and JMJD6 confers a more aggressive phenotype in mouse and human tumors. Given the pleiotropic pro-tumorigenic activities of JMJD6, it may be useful as a prognostic factor and a therapeutic target for Myc-driven mammary tumorigenesis.

Indexed as

Epigenesis, GeneticAnimalsApoptosisBreast NeoplasmsCell Line, TumorCell Transformation, NeoplasticComparative Genomic HybridizationFemaleGene Expression Regulation, NeoplasticHumansJumonji Domain-Containing Histone DemethylasesMammary Neoplasms, ExperimentalMiceNeoplasm MetastasisPrognosisProto-Oncogene Proteins c-mycJMJD6 protein, humanJumonji Domain-Containing Histone DemethylasesMYC protein, humanProto-Oncogene Proteins c-mycCopy number variantsEpigeneticsJMJD6Mammary cancerMycTumor progression

Identifiers

PMID27081402
PMCPMC4831179
OpenAlexW2341628771

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.