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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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The expression of RBP2 and miR-21 in 26 patients with chronic myeloid leukemia in the chronic phase (CML-CP) and in 18 with blastic phase (CML-BP)(A, B) qRT-PCR and IHC analysis of RBP2 mRNA and protein levels. Data are mean ± SEM. (C) qRT-PCR analysis of the relative expression of mature miR-21 in CML-CP patients and CML-BP patients. Human CML-CP and -BP cells were from bone marrow of patients. Data are mean ± SEM. The results were confirmed by 3 independent experiments. *P< 0.05.
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Figure 7: The expression of RBP2 and miR-21 in 26 patients with chronic myeloid leukemia in the chronic phase (CML-CP) and in 18 with blastic phase (CML-BP)(A, B) qRT-PCR and IHC analysis of RBP2 mRNA and protein levels. Data are mean ± SEM. (C) qRT-PCR analysis of the relative expression of mature miR-21 in CML-CP patients and CML-BP patients. Human CML-CP and -BP cells were from bone marrow of patients. Data are mean ± SEM. The results were confirmed by 3 independent experiments. *P< 0.05.

Mentions: To investigate whether RBP2 was critical in CML progression, we measured RBP2 mRNA and protein levels in bone-marrow samples from patients with newly diagnosed CML-CP or CML-BP. The clinical characteristics of CML patients are in Table 1. RBP2 mRNA and protein levels were lower in CML-BP than CML-CP samples (Figure 7A, B). Therefore, RBP2 is underexpressed during CML progression. miR-21 level was higher in CML-BP than CML-CP samples (Figure 7C).


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)

The expression of RBP2 and miR-21 in 26 patients with chronic myeloid leukemia in the chronic phase (CML-CP) and in 18 with blastic phase (CML-BP)(A, B) qRT-PCR and IHC analysis of RBP2 mRNA and protein levels. Data are mean ± SEM. (C) qRT-PCR analysis of the relative expression of mature miR-21 in CML-CP patients and CML-BP patients. Human CML-CP and -BP cells were from bone marrow of patients. Data are mean ± SEM. The results were confirmed by 3 independent experiments. *P< 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: The expression of RBP2 and miR-21 in 26 patients with chronic myeloid leukemia in the chronic phase (CML-CP) and in 18 with blastic phase (CML-BP)(A, B) qRT-PCR and IHC analysis of RBP2 mRNA and protein levels. Data are mean ± SEM. (C) qRT-PCR analysis of the relative expression of mature miR-21 in CML-CP patients and CML-BP patients. Human CML-CP and -BP cells were from bone marrow of patients. Data are mean ± SEM. The results were confirmed by 3 independent experiments. *P< 0.05.
Mentions: To investigate whether RBP2 was critical in CML progression, we measured RBP2 mRNA and protein levels in bone-marrow samples from patients with newly diagnosed CML-CP or CML-BP. The clinical characteristics of CML patients are in Table 1. RBP2 mRNA and protein levels were lower in CML-BP than CML-CP samples (Figure 7A, B). Therefore, RBP2 is underexpressed during CML progression. miR-21 level was higher in CML-BP than CML-CP samples (Figure 7C).

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