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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Apoptosis Regulatory Proteins
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Blast Crisis / genetics*
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Blast Crisis / metabolism
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Blotting, Western
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Cell Differentiation / genetics
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Cell Proliferation / genetics
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Female
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Gene Expression Regulation, Leukemic*
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HL-60 Cells
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Histones / metabolism
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Humans
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K562 Cells
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Male
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MicroRNAs / genetics*
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Middle Aged
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Promoter Regions, Genetic / genetics
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Protein Binding
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RNA-Binding Proteins
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Retinoblastoma-Binding Protein 2 / genetics*
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Retinoblastoma-Binding Protein 2 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Apoptosis Regulatory Proteins
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Histones
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MIRN21 microRNA, human
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MicroRNAs
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PDCD4 protein, human
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RNA-Binding Proteins
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KDM5A protein, human
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Retinoblastoma-Binding Protein 2