Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia.

Minran Zhou, Jiping Zeng, Xiaoming Wang, Xiangyu Wang, Tao Huang, Yue Fu, Ting Sun, Jihui Jia, Chunyan Chen

Journal: Oncotarget 2015;6(2):1249-61

PMID: 25575817

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Abstract

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.

Address: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.; Department of Biochemistry, School of Medicine, Shandong University, Jinan, Shandong, P. R. China.; Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, Shandong, P. R. China.

DOI: 10.18632/oncotarget.2859

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MeSH Terms: Adult, Aged, Aged, 80 and over, Apoptosis Regulatory Proteins, Blast Crisis, Blotting, Western, Cell Differentiation, Cell Proliferation, Female, Gene Expression Regulation, Leukemic, HL-60 Cells, Histones, Humans, K562 Cells, Male, MicroRNAs, Middle Aged, Promoter Regions, Genetic, Protein Binding, RNA-Binding Proteins, Retinoblastoma-Binding Protein 2, Reverse Transcriptase Polymerase Chain Reaction