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

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 t...

Full description

Saved in:
Bibliographic Details
Published in:Oncogene 2015-01, Vol.34 (2), p.257-262
Main Authors: Parrish, J K, Sechler, M, Winn, R A, Jedlicka, P
Format: Article
Language:English
Subjects:
631/337/176
631/337/384/331
631/67/1798
692/420/755
Analysis
Animals
Apoptosis
Bone Neoplasms - enzymology
Bone Neoplasms - genetics
Bones
Care and treatment
Cell Biology
Cell Line, Tumor
Cell Transformation, Neoplastic - genetics
Diagnosis
Down-Regulation
Epigenetic inheritance
Epigenomics
Ewing's sarcoma
Ewings sarcoma
Genetic aspects
Heterografts
Human Genetics
Humans
Internal Medicine
Jumonji Domain-Containing Histone Demethylases - genetics
Jumonji Domain-Containing Histone Demethylases - metabolism
Malignancy
Medicine
Medicine & Public Health
Mice
Mice, Nude
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Oncology
Ribonucleic acid
RNA
Sarcoma
Sarcoma, Ewing - enzymology
Sarcoma, Ewing - genetics
Sarcoma, Ewing - pathology
short-communication
Tissues
Tumorigenesis
Tumors
Xenografts
Young adults
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2013.541