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

Abstract

// Minran Zhou 1 , Jiping Zeng 2 , Xiaoming Wang 1 , Xiangyu Wang 1 , Tao Huang 1 , Yue Fu 1 , Ting Sun 1 , Jihui Jia 3 and Chunyan Chen 1 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 Correspondence: Chunyan Chen, email: // Keywords : RBP2; miR-21; chronic myeloid leukemia; blast crisis Received : August 22, 2014 Accepted : November 25, 2014 Published : November 26, 2014 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.