Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia
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Minran Zhou1, Jiping Zeng2, Xiaoming Wang1, Xiangyu Wang1, Tao Huang1, Yue Fu1, Ting Sun1, Jihui Jia3 and Chunyan Chen1
1 Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China
2 Department of Biochemistry, School of Medicine, Shandong University, Jinan, Shandong, P. R. China
3 Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, Shandong, P. R. China
Chunyan Chen, email:
Keywords: RBP2; miR-21; chronic myeloid leukemia; blast crisis
Received: August 22, 2014 Accepted: November 25, 2014 Published: November 26, 2014
Chronic myeloid leukemia in the blastic phase (CML-BP) responds poorly to clinical treatments and is usually fatal. In this study, we found that the histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is underexpressed in CML-BP. The RBP2 histone demethylase stimulates leukemia cell differentiation and inhibits cell proliferation. We identified miR-21 was directly downregulated by RBP2 and found that miR-21 downregulated PDCD4 expression in leukemia cells. By binding to miR-21 promoter and by demethylating of trimethylated H3K4 at the miR-21 locus, RBP2 downregulated miR-21 expression. This in turn activated PDCD4. In conclusion, RBP2 epigenetically downregulated miR-21 in blast transformation of CML.
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