Journal
ONCOTARGET
Volume 6, Issue 2, Pages 1249-1261Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2859
Keywords
RBP2; miR-21; chronic myeloid leukemia; blast crisis
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB911202]
- National Natural Science Foundation of China [81470318, 81170514, 30971151]
- project of Shandong province science and technology development plans [2014GSF118114]
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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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