ArticleJournal of translational medicine2014
Epigenetic inactivation of mir-34b/c in addition to mir-34a and DAPK1 in chronic lymphocytic leukemia.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- An updated meta-analysis of 23 case-control studies on the association between miR-34b/c polymorphism and cancer risk.Oncotarget · 2017Pooled it
- Death-associated protein kinase 1: a double-edged sword in health and disease.Frontiers in immunology · 2025Review
- Article
- Role of microRNAs in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2023Review
- Transcriptional Activity of Some Genes Involved in Apoptosis in Patients with Vulvar Lichen Sclerosus.Bulletin of experimental biology and medicine · 2022Article
- Investigation the Cytotoxicity of 5-AZA on Acute Lymphoblastic Leukemia Cell Line In Vitro and Characterization the Underlying Molecular Mechanisms of Cell Death and Motility.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Review
- Chidamide acts on the histone deacetylase-mediated miR-34a/Bcl-2 axis to regulate NB4 cell line proliferation and apoptosis.The Kaohsiung journal of medical sciences · 2020Article
- DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2020Article
- Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL.Genome medicine · 2020Article
- Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals.Frontiers in oncology · 2020Review
- PD-L1 and miR-34a are Prognostic Factors for Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP.Cancer management and research · 2020Article
- MicroRNA miR-34a downregulates FOXP1 during DNA damage response to limit BCR signalling in chronic lymphocytic leukaemia B cells.Leukemia · 2019Article
- Hypermethylation of miR-34b/c is associated with early clinical stages and tumor differentiation in Kazakh patients with esophageal squamous cell carcinoma.International journal of clinical and experimental pathology · 2019Article
- Impact Of TP53 Gene Promoter Methylation On Chronic Lymphocytic Leukemia Pathogenesis And Progression.Journal of blood medicine · 2019Article
- Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.Leukemia · 2019Article
- Analysis of the miR-34 family functions in breast cancer reveals annotation error of miR-34b.Scientific reports · 2017Article
- The effects of microRNAs on glucocorticoid responsiveness.Journal of cancer research and clinical oncology · 2017Review
- Altered expression of miRNAs and methylation of their promoters are correlated in neuroblastoma.Oncotarget · 2016Article
- Epigenetic silencing of tumor suppressor long non-coding RNA BM742401 in chronic lymphocytic leukemia.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTP53 mutation/deletion is uncommon in chronic lymphocytic leukemia (CLL). We postulated that components of TP53-centered tumor suppressor network, miR-34b/c, in addition to DAPK1 and miR-34a might be inactivated by DNA hypermethylation. Moreover, we tested if miR-34b/c methylation might correlate with miR-203 or miR-124-1 methylation in CLL.
methodsmiR-34b/c, miR-34a and DAPK1 methylation was studied in 11 normal controls, 7 CLL cell lines, and 78 diagnostic CLL samples by methylation-specific polymerase chain reaction. MEC-1 cells were treated with 5-Aza-2'-deoxycytidine for reversal of methylation-associated miRNA silencing. Tumor suppressor properties of miR-34b were demonstrated by over-expression of precursor miR-34b in MEC-1 cells.
resultsmiR-34b/c promoter was unmethylated in normal controls, but completely methylated in 4 CLL cell lines. miR-34b/c expression was inversely correlated with miR-34b/c methylation. Different MSP statuses of miR-34b/c, including complete methylation and complete unmethylation, were verified by quantitative bisulfite pyrosequencing. 5-Aza-2'-deoxycytidine treatment resulted in promoter demethylation and miR-34b re-expression in MEC1 cells. Moreover, over-expression of miR-34b resulted in inhibition of cellular proliferation and increased cell death. In primary CLL samples, miR-34a, miR-34b/c and DAPK1 methylation was detected in 2.6%, 17.9% and 34.6% of patients at diagnosis respectively. Furthermore, 39.7%, 3.8% and 2.6% patients had methylation of one, two or all three genes respectively. Overall, 46.2% patients had methylation of at least one of these three genes. Besides, miR-34b/c methylation was associated with methylation of miR-34a (P = 0.03) and miR-203 (P = 0.012) in CLL.
conclusionsTaken together, miR-34b/c is a tumor suppressor miRNA frequently methylated, and hence silenced in CLL. Together with DAPK1 methylation, miR-34b/c methylation is implicated in the disruption of the TP53-centered tumor suppressor network. Moreover, the association of miRNA methylation warrants further study.
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