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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 08, 2017 |
| Title |
The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of the bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. Our laboratory has previously identified the Jumonji-domain H3K9 me 1/2 histone demethylase KDM3A as a novel oncogene downstream of EWS/Fli1, the most common oncofusion in Ewing Sarcoma. Herein, we uncover a role for KDM3A in the promotion of Ewing Sarcoma metastasis.
Using global gene expression profiling, we show that some of the most strongly regulated genes by KDM3A are those implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and metastasis in vivo. We further provide evidence that MCAM, one of the most strongly and consistently regulated genes by KDM3A, is an important effector of KDM3A pro-metastatic action. Our studies also show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor.
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| Overall design |
Biological triplicates of A673 cells were stably transduced with Scrambled shRNA control, or 1 of 2 different KDM3A knockdown shRNA sequences (KDM3A sh1 or sh2) for RNA extraction and hybridization on Affymetrix microarrays.
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| Contributor(s) |
Sechler M, Parrish JK, Birks DK, Jedlicka P |
| Citation(s) |
28319067 |
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| Submission date |
Feb 07, 2017 |
| Last update date |
May 10, 2017 |
| Contact name |
Paul Jedlicka |
| Organization name |
University of Colorado Denver Anschutz Medical Campus
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| Department |
Pathology, MS-8104
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| Street address |
12800 E 19th Ave
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| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (9)
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| GSM2479402 |
scrambled control shRNA, biological rep 1 |
| GSM2479403 |
scrambled control shRNA, biological rep 2 |
| GSM2479404 |
scrambled control shRNA, biological rep 3 |
| GSM2479405 |
KDM3A knockdown using shRNA 1, biological rep 1 |
| GSM2479406 |
KDM3A knockdown using shRNA 1, biological rep 2 |
| GSM2479407 |
KDM3A knockdown using shRNA 1, biological rep 3 |
| GSM2479408 |
KDM3A knockdown using shRNA 2, biological rep 1 |
| GSM2479409 |
KDM3A knockdown using shRNA 2, biological rep 2 |
| GSM2479410 |
KDM3A knockdown using shRNA 2, biological rep 3 |
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| Relations |
| BioProject |
PRJNA371619 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94619_RAW.tar |
36.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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