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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

A summary of the findingsA new epigenetic mechanism involved in the pathogenesis of CML-BP: by binding to promoter and demethylation of trimethylated H3K4 at the miR-21 locus, RBP2 downregulates miR-21 expression, which in turn activates PDCD4. In CML progression, low levels of RBP2 cannot repress the expression of miR-21, which decreases PDCD4 expression to block cell differentiation and stimulate cell proliferation.
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Figure 8: A summary of the findingsA new epigenetic mechanism involved in the pathogenesis of CML-BP: by binding to promoter and demethylation of trimethylated H3K4 at the miR-21 locus, RBP2 downregulates miR-21 expression, which in turn activates PDCD4. In CML progression, low levels of RBP2 cannot repress the expression of miR-21, which decreases PDCD4 expression to block cell differentiation and stimulate cell proliferation.

Mentions: Overall, we found a new epigenetic mechanism involved in the pathogenesis of CML-BP (Figure 8). Because CML-BP responds poorly to treatment and is usually fatal, we need to uncover mechanisms and find new drug targets. Here we found that the histone demethylase RBP2 is underexpressed in CML-BP. Low RBP2 expression could not repress miR-21 expression, which promoted the transition of CML from CP to BP. RBP2 could be a useful biological marker in CML progression.


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)

A summary of the findingsA new epigenetic mechanism involved in the pathogenesis of CML-BP: by binding to promoter and demethylation of trimethylated H3K4 at the miR-21 locus, RBP2 downregulates miR-21 expression, which in turn activates PDCD4. In CML progression, low levels of RBP2 cannot repress the expression of miR-21, which decreases PDCD4 expression to block cell differentiation and stimulate cell proliferation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: A summary of the findingsA new epigenetic mechanism involved in the pathogenesis of CML-BP: by binding to promoter and demethylation of trimethylated H3K4 at the miR-21 locus, RBP2 downregulates miR-21 expression, which in turn activates PDCD4. In CML progression, low levels of RBP2 cannot repress the expression of miR-21, which decreases PDCD4 expression to block cell differentiation and stimulate cell proliferation.
Mentions: Overall, we found a new epigenetic mechanism involved in the pathogenesis of CML-BP (Figure 8). Because CML-BP responds poorly to treatment and is usually fatal, we need to uncover mechanisms and find new drug targets. Here we found that the histone demethylase RBP2 is underexpressed in CML-BP. Low RBP2 expression could not repress miR-21 expression, which promoted the transition of CML from CP to BP. RBP2 could be a useful biological marker in CML progression.

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