KDM3B shows tumor-suppressive activity and transcriptionally regulates HOXA1 through retinoic acid response elements in acute myeloid leukemia.

Autor: Xu X; a Laboratory for Stem Cell and Regenerative Medicine , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China., Nagel S; b Department of Human and Animal Cell Culture , Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures , Braunschweig , Germany., Quentmeier H; b Department of Human and Animal Cell Culture , Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures , Braunschweig , Germany., Wang Z; c Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China., Pommerenke C; b Department of Human and Animal Cell Culture , Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures , Braunschweig , Germany., Dirks WG; b Department of Human and Animal Cell Culture , Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures , Braunschweig , Germany., Macleod RAF; b Department of Human and Animal Cell Culture , Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures , Braunschweig , Germany., Drexler HG; b Department of Human and Animal Cell Culture , Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures , Braunschweig , Germany., Hu Z; a Laboratory for Stem Cell and Regenerative Medicine , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.; c Department of Hematology , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong , China.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2018 Jan; Vol. 59 (1), pp. 204-213. Date of Electronic Publication: 2017 May 25.
DOI: 10.1080/10428194.2017.1324156
Abstrakt: 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 with 5q deletion. We then performed global microarray profiling to identify potential downstream targets of KDM3B, notably HOXA1, 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 of HOXA1 gene. KDM3B knockdown resulted in increased mono-methylation but decreased di-methylation of H3K9 at RARE while eschewing the promoter region of HOXA1. Collectively, we found that KDM3B exhibits potential tumor-suppressive activity and transcriptionally modulates HOXA1 expression via RARE in AML.
Databáze: MEDLINE
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