title: Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia.
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.
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Minran
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, School of Medicine, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D001752:Blast Crisis / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016601:RNA-Binding Proteins; D056485:Retinoblastoma-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; D006657:Histones; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C070050:KDM5A protein, human; D056485:Retinoblastoma-Binding Protein 2