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

Zhou M, Zeng J, Wang X, Wang X, Huang T, Fu Y, Sun T, Jia J, Chen C - Oncotarget (2015)

Bottom Line: In this study, we found that the histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is underexpressed in CML-BP.This in turn activated PDCD4.In conclusion, RBP2 epigenetically downregulated miR-21 in blast transformation of CML.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.

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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Related in: MedlinePlus

RBP2 inhibits the cell proliferation(A) Western blot analysis of protein level of RBP2 with RBP2 expression plasmid. β-actin was a loading control. (B, C) Proliferation of K562 and HL60 cells after transfection with RBP2 expression plasmid. (D, E) Foci formation of K562 and HL60 cells after transfection with RBP2 expression plasmid. The results are from 3 independent experiments. *P< 0.05, **P< 0.01.
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Figure 2: RBP2 inhibits the cell proliferation(A) Western blot analysis of protein level of RBP2 with RBP2 expression plasmid. β-actin was a loading control. (B, C) Proliferation of K562 and HL60 cells after transfection with RBP2 expression plasmid. (D, E) Foci formation of K562 and HL60 cells after transfection with RBP2 expression plasmid. The results are from 3 independent experiments. *P< 0.05, **P< 0.01.

Mentions: We explored the potential role of RBP2 in leukemia cell proliferation by transfecting RBP2 expression plasmid into K562 and HL60 cells. RBP2 protein level was increased significantly in K562 and HL60 cells (Figure 2A). As well, K562 and HL60 cells transfected with RBP2 expression plasmid proliferated at a slower rate than with vector transfection (Figure 2B, C), and their colony-formation ability was impaired (Figure 2D, E). Thus, RBP2 inhibited proliferation of leukemia cells.


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

Zhou M, Zeng J, Wang X, Wang X, Huang T, Fu Y, Sun T, Jia J, Chen C - Oncotarget (2015)

RBP2 inhibits the cell proliferation(A) Western blot analysis of protein level of RBP2 with RBP2 expression plasmid. β-actin was a loading control. (B, C) Proliferation of K562 and HL60 cells after transfection with RBP2 expression plasmid. (D, E) Foci formation of K562 and HL60 cells after transfection with RBP2 expression plasmid. The results are from 3 independent experiments. *P< 0.05, **P< 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359230&req=5

Figure 2: RBP2 inhibits the cell proliferation(A) Western blot analysis of protein level of RBP2 with RBP2 expression plasmid. β-actin was a loading control. (B, C) Proliferation of K562 and HL60 cells after transfection with RBP2 expression plasmid. (D, E) Foci formation of K562 and HL60 cells after transfection with RBP2 expression plasmid. The results are from 3 independent experiments. *P< 0.05, **P< 0.01.
Mentions: We explored the potential role of RBP2 in leukemia cell proliferation by transfecting RBP2 expression plasmid into K562 and HL60 cells. RBP2 protein level was increased significantly in K562 and HL60 cells (Figure 2A). As well, K562 and HL60 cells transfected with RBP2 expression plasmid proliferated at a slower rate than with vector transfection (Figure 2B, C), and their colony-formation ability was impaired (Figure 2D, E). Thus, RBP2 inhibited proliferation of leukemia cells.

Bottom Line: In this study, we found that the histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is underexpressed in CML-BP.This in turn activated PDCD4.In conclusion, RBP2 epigenetically downregulated miR-21 in blast transformation of CML.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China.

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.

Show MeSH
Related in: MedlinePlus