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| Status |
Public on Nov 17, 2018 |
| Title |
Expression data from DU145 prostate cancer cells treated with DHA or DMSO |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to increase in resistance to drug therapy. Here, we have evaluated a library of natural compounds for inhibitors of Axl. We identified dihydroartemisin (DHA), the active principle of the anti-malarial drug artemisinin, as a specific Axl inhibitor in prostate cancer (PCa). DHA blocks Axl expression leading to apoptosis induction, decrease in cell proliferation, migration and tumor development of PCa cells. Furthermore, DHA treatment synergizes with docetaxel, a standard of care in metastatic PCa, and increases the overall survival of mice with human PCa xenografts. We demonstrated that DHA-mediated control of miR-34a and miR-7 expression leads to inhibition of Axl expression. This process is dependent on regulation of the chromatin via methylation of histone H3 lysine 27 residues (H3K27) by Jumonji, AT-rich interaction domain containing 2 (JARID2) and the enhancer of zeste homolog 2 (EZH2), components of the Polycomb Complex Repressor 2 (PCR2). Our discovery of a previously unidentified miR-34a/miR-7/JARID2 pathway that controls DHA-mediated effects on Axl expression and inhibition of cancer cell proliferation, migration, invasion and tumor formation provides new molecular and mechanistic insights into DHA’s anti-cancer effect on PCa with potential therapeutic implications.
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| Overall design |
Total RNA was isolated from DU145treated with 5μM DHA or vehicle control (DMSO) for 6 hours and hybridized to HT Human U133 gene .
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| Contributor(s) |
Bashin M, Libermann T, Gu X |
| Citation(s) |
30783079 |
| Submission date |
Nov 16, 2018 |
| Last update date |
Feb 22, 2019 |
| Contact name |
Luiz F Zerbini |
| E-mail(s) |
luiz.zerbini@icgeb.org
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| Organization name |
ICGEB
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| Lab |
Cancer Genomics
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| Street address |
Wernher and Beit Building (South), Anzio Road
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| City |
Cape Town |
| ZIP/Postal code |
7925 |
| Country |
South Africa |
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| Platforms (1) |
| GPL13158 |
[HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA505804 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122625_RAW.tar |
8.0 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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