Oncotarget

Research Papers:

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 and Chunyan Chen _

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Oncotarget. 2015; 6:1249-1261. https://doi.org/10.18632/oncotarget.2859

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Abstract

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

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.


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