RGD Reference Report - The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing Sarcoma. - Rat Genome Database

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The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing Sarcoma.

Authors: Parrish, JK  Sechler, M  Winn, RA  Jedlicka, P 
Citation: Parrish JK, etal., Oncogene. 2013 Dec 23. doi: 10.1038/onc.2013.541.
RGD ID: 9590218
Pubmed: PMID:24362521   (View Abstract at PubMed)
PMCID: PMC4477825   (View Article at PubMed Central)
DOI: DOI:10.1038/onc.2013.541   (Journal Full-text)

Ewing Sarcoma is a biologically aggressive bone and soft tissue malignancy affecting children and young adults. Ewing Sarcoma pathogenesis is driven by EWS/Ets fusion oncoproteins, of which EWS/Fli1 is the most common. We have previously shown that microRNAs (miRs) regulated by EWS/Fli1 contribute to the pro-oncogenic program in Ewing Sarcoma. Here we show that miR-22, an EWS/Fli1-repressed miR, is inhibitory to Ewing Sarcoma clonogenic and anchorage-independent cell growth, even at modest overexpression levels. Our studies further identify the H3K9me1/2 histone demethylase KDM3A (JMJD1A/JHDM2A) as a new miR-22-regulated gene. We show that KDM3A is overexpressed in Ewing Sarcoma, and that its depletion inhibits clonogenic and anchorage-independent growth in multiple patient-derived cell lines, and tumorigenesis in a xenograft model. KDM3A depletion further results in augmentation of the levels of the repressive H3K9me2 histone mark, and downregulation of pro-oncogenic factors in Ewing Sarcoma. Together, our studies identify the histone demethylase KDM3A as a new, miR-regulated, tumor promoter in Ewing Sarcoma.Oncogene advance online publication, 23 December 2013; doi:10.1038/onc.2013.541.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ewing sarcoma  IEP 9590218mRNA:increased expression:bone marrow (human)RGD 
Ewing sarcoma  ISOKDM3A (Homo sapiens)9590218; 9590218mRNA:increased expression:bone marrow (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm3a  (lysine demethylase 3A)

Genes (Mus musculus)
Kdm3a  (lysine (K)-specific demethylase 3A)

Genes (Homo sapiens)
KDM3A  (lysine demethylase 3A)


Additional Information