ArticleMolecular cancer2013
Epigenetic inactivation of miR-9 family microRNAs in chronic lymphocytic leukemia--implications on constitutive activation of NFκB pathway.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
- A Comparative Analysis of the Methylation Status of Non-Coding RNA Promoters in Fibroid and Matched Myometrium.International journal of molecular sciences · 2026Article
- The Role of MicroRNAs, CircRNAs, and LncRNAs in Chronic Lymphocytic Leukemia.Current pharmaceutical design · 2025Review
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- MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia.EJHaem · 2024Review
- AL amyloidosis clonal plasma cells are regulated by microRNAs and dependent on anti-apoptotic BCL2 family members.Cancer medicine · 2023Article
- miRNAs in Lymphocytic Leukaemias-The miRror of Drug Resistance.International journal of molecular sciences · 2022Review
- Regulatory role of miRNAs in Wnt signaling pathway linked with cardiovascular diseases.Current research in pharmacology and drug discovery · 2022Article
- Crosstalk Between Inflammatory Signaling and Methylation in Cancer.Frontiers in cell and developmental biology · 2021Review
- Epigenetic silencing of miR-342-3p in B cell lymphoma and its impact on autophagy.Clinical epigenetics · 2020Article
- The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation.Molecular therapy. Nucleic acids · 2020Review
- Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm.Cancer medicine · 2020Article
- Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL.Genome medicine · 2020Article
- Role of microRNA in inner ear stem cells and related research progress.American journal of stem cells · 2020Review
- Epigenetic silencing of long non-coding RNACancer cell international · 2020Article
- Epigenetic silencing of miR-340-5p in multiple myeloma: mechanisms and prognostic impact.Clinical epigenetics · 2019Article
- Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks.International journal of molecular sciences · 2019Review
- Sulforaphane epigenetically demethylates the CpG sites of the miR-9-3 promoter and reactivates miR-9-3 expression in human lung cancer A549 cells.The Journal of nutritional biochemistry · 2018Article
- The versatile nature of miR-9/9Oncotarget · 2018Review
- MicroRNA signatures and Foxp3Oncotarget · 2018Article
- Epigenetic silencing of LPP/miR-28 in multiple myeloma.Journal of clinical pathology · 2018Article
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Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe miR-9 family microRNAs have been identified as a tumor suppressor miRNA in cancers. We postulated that miR-9-1, miR-9-2 and miR-9-3 might be inactivated by DNA hypermethylation in chronic lymphocytic leukemia (CLL).
methodsMethylation of miR-9-1, miR-9-2 and miR-9-3 was studied in eight normal controls including normal bone marrow, buffy coat, and CD19-sorted peripheral blood B-cells from healthy individuals, seven CLL cell lines, and seventy-eight diagnostic CLL samples by methylation-specific polymerase chain reaction.
resultsThe promoters of miR-9-3 and miR-9-1 were both unmethylated in normal controls, but methylated in five (71.4%) and one of seven CLL cell lines respectively. However, miR-9-2 promoter was methylated in normal controls including CD19 + ve B-cells, hence suggestive of a tissue-specific but not tumor-specific methylation, and thus not further studied. Different MSP statuses of miR-9-3, including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite methylation analysis. 5-Aza-2'-deoxycytidine treatment resulted in miR-9-3 promoter demethylation and re-expression of pri-miR-9-3 in I83-E95 and WAC3CD5+ cells, which were homozygously methylated for miR-9-3. Moreover, overexpression of miR-9 led to suppressed cell proliferation and enhanced apoptosis together with downregulation of NFκB1 in I83-E95 cells, supporting a tumor suppressor role of miR-9-3 in CLL. In primary CLL samples, miR-9-3 was detected in 17% and miR-9-1 methylation in none of the patients at diagnosis. Moreover, miR-9-3 methylation was associated with advanced Rai stage (≥ stage 2) (P = 0.04).
conclusionsOf the miR-9 family, miR-9-3 is a tumor suppressor miRNA relatively frequently methylated, and hence silenced in CLL; whereas miR-9-1 methylation is rare in CLL. The role of miR-9-3 methylation in the constitutive activation of NFκB signaling pathway in CLL warrants further study.
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