ArticlePloS one2014
The KDM2B- let-7b -EZH2 axis in myelodysplastic syndromes as a target for combined epigenetic therapy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Deciphering the role of LOC124905135-related non-coding RNA cluster in human cancers: A comprehensive review.Heliyon · 2024Review
- Article
- The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies.Biomolecules · 2021Review
- Inhibition of microRNA let-7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer.Cancer science · 2021Article
- Regulation of Normal and Malignant Hematopoiesis by FBOX Ubiquitin E3 Ligases.Trends in immunology · 2020Review
- m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation.Oncology reports · 2020Observational
- Microarray analysis of differentially expressed microRNAs in myelodysplastic syndromes.Medicine · 2020Article
- Association of EZH2 protein expression by immunohistochemistry in myelodysplasia related neoplasms with mutation status, cytogenetics and clinical outcomes.British journal of haematology · 2019Article
- MicroRNA-Dependent Regulation of IGF1R Gene Expression in Hormone-Sensitive and Hormone-Resistant Prostate Cancer Cells.Doklady. Biochemistry and biophysics · 2018Article
- Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B.Molecular oncology · 2018Article
- KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth.OncoTargets and therapy · 2018Article
- Histone demethylase KDM2B upregulates histone methyltransferase EZH2 expression and contributes to the progression of ovarian cancer in vitro and in vivo.OncoTargets and therapy · 2017Article
- Down-regulation of EZH2 expression in myelodysplastic syndromes.Leukemia research · 2016Article
- Genomic loss of EZH2 leads to epigenetic modifications and overexpression of the HOX gene clusters in myelodysplastic syndrome.Oncotarget · 2016Article
- Article
- Histone demethylase KDM2B inhibits the chondrogenic differentiation potentials of stem cells from apical papilla.International journal of clinical and experimental medicine · 2015Article
- Noncoding RNAs and Their Response Predictive Value in Azacitidine-treated Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia With Myelodysplasia-related Changes.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Both DNA and histone methylation are dysregulated in the myelodysplastic syndromes (MDS). Based on preliminary data we hypothesized that dysregulated interactions of KDM2B, let-7b and EZH2 signals lead to an aberrant epigenetic landscape. Gene expression in CD34+ cells from MDS marrows was analyzed by NanoString miR array and validated by real-time polymerase chain reaction (PCR). The functions of KDM2B, let-7b and EZH2 were characterized in myeloid cell lines and in primary MDS cells. Let-7b levels were significantly higher, and KDM2B and EZH2 expression was lower in primary CD34+ MDS marrow cells (n = 44) than in healthy controls (n = 21; p<0.013, and p<0.0001, respectively). Overexpression of let-7b reduced EZH2 and KDM2B protein levels, and decreased cells in S-phase while increasing G0/G1 cells (p = 0.0005), accompanied by decreased H3K27me3 and cyclin D1. Silencing of KDM2B increased let-7b expression. Treatment with the cyclopentanyl analog of 3-deazaadenosine, DZNep, combined with the DNA hypomethylating agent 5-azacitidine, decreased levels of EZH2, suppressed methylation of di- and tri-methylated H3K27, and increased p16 expression, associated with cell proliferation. Thus, KDM2B, via let-7b/EZH2, promotes transcriptional repression. DZNep bypassed the inhibitory KDM2B/let-7b/EZH2 axis by preventing H3K27 methylation and reducing cell proliferation. DZNep might be able to enhance the therapeutic effects of DNA hypomethylating agents such as 5-azacitidine, currently considered standard therapy for patients with MDS.
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