1. KDM3B shows tumor-suppressive activity and transcriptionally regulates HOXA1 through retinoic acid response elements in acute myeloid leukemia.
- Author
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Xu, Xin, Nagel, Stefan, Quentmeier, Hilmar, Wang, Zhanju, Pommerenke, Claudia, Dirks, Wilhelm G., Macleod, Roderick A. F., Drexler, Hans G., and Hu, Zhenbo
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ACUTE myeloid leukemia , *ACUTE myeloid leukemia treatment , *GENE expression , *METHYLATION kinetics , *CANCER cell analysis , *PATIENTS - Abstract
KDM3B reportedly shows both tumor-suppressive and tumor-promoting activities in leukemia. The function of KDM3B is likely cell-type dependent and its seeming functional discordance may reflect its phenotypic dependence on downstream targets. Here, we first showed the underexpression of KDM3B in acute myeloid leukemia (AML) patients and AML cell lines with MLL-AF6/9 or PML-RARA translocations. Overexpression of KDM3B repressed colony formation of AML cell line with5qdeletion. We then performed global microarray profiling to identify potential downstream targets of KDM3B, notablyHOXA1, which was verified by real time PCR and Western blotting. We further showed KDM3B binding at retinoic acid response elements (RARE) but not at the promoter region ofHOXA1gene. KDM3B knockdown resulted in increased mono-methylation but decreased di-methylation of H3K9 at RARE while eschewing the promoter region ofHOXA1. Collectively, we found that KDM3B exhibits potential tumor-suppressive activity and transcriptionally modulates HOXA1 expressionviaRARE in AML. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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