Transcriptomics

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Expression data from DU145 prostate cancer cells treated with DHA or DMSO


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122625 | GEO | 2018/11/17

REPOSITORIES: GEO

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