ArticlePLoS genetics2013
Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the In Cis downregulation of a gene cluster that targets NF-kB.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns.Journal of medical genetics · 2019Pooled it
- A Comprehensive Guide on Epigenetics' Precision Role in Uncommon "Rare" Cancers' Biology and Treatment Frontiers.Sub-cellular biochemistry · 2026Review
- Roles of Long Non-Coding RNAs in the Pathogenesis of Cardiovascular Disorders: Challenges and Opportunities.Journal of cardiovascular translational research · 2025Review
- Identifying lncRNA-Protein Interactions in Hematopoietic Progenitor Cells by Hybridization Capture and Mass Spectrometry.Journal of proteome research · 2025Article
- Olfactory receptor OR51B5 suppressed esophageal cancer progression through activates Calcium / N-Ras signaling.Cell death & disease · 2025Article
- Non-coding RNAs as a Critical Player in the Regulation of Inflammasome in Inflammatory Bowel Diseases; Emphasize on lncRNAs.Cell biochemistry and biophysics · 2025Review
- Interplay between LncRNAs and autophagy-related pathways in leukemia: mechanisms and clinical implications.Medical oncology (Northwood, London, England) · 2025Review
- Physiological and cellular mechanisms of ischemic preconditioning microRNAs-mediated in underlying of ischemia/reperfusion injury in different organs.Molecular and cellular biochemistry · 2025Review
- High Expression Levels of the Long Non-Coding RNAs Lnc-IRF2-3 and Lnc-KIAA1755-4 Are Markers of Poor Prognosis in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2025Article
- The Role of MicroRNAs, CircRNAs, and LncRNAs in Chronic Lymphocytic Leukemia.Current pharmaceutical design · 2025Review
- Multiple omics levels of chronic lymphocytic leukemia.Cell death discovery · 2024Review
- Advances in epigenetic alterations of chronic lymphocytic leukemia: from pathogenesis to treatment.Clinical and experimental medicine · 2024Review
- Long noncoding RNA DLEU2 and ROR1 pathway induces epithelial-to-mesenchymal transition and cancer stem cells in breast cancer.Cell death discovery · 2024Article
- Deleted in lymphocytic leukemia 2 (DLEU2): a possible biomarker that holds promise for future diagnosis and treatment of cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Transcriptional repression of lncRNA and miRNA subsets mediated by LRF during erythropoiesis.Journal of molecular medicine (Berlin, Germany) · 2023Article
- The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers.Genomics, proteomics & bioinformatics · 2023Article
- Investigation of Flavonoid Scaffolds as DAX1 Inhibitors against Ewing Sarcoma through Pharmacoinformatic and Dynamic Simulation Studies.International journal of molecular sciences · 2023Article
- Identification and Validation of Ferroptosis-Related LncRNAs Signature as a Novel Prognostic Model for Chronic Lymphocytic Leukemia.International journal of general medicine · 2023Article
- Overexpression of lncRNA DLEU1 in Gastric Cancer Tissues Compared to Adjacent Non-Tumor Tissues.Journal of gastrointestinal cancer · 2022Article
- Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia.Life (Basel, Switzerland) · 2022Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-coding RNAs are much more common than previously thought. However, for the vast majority of non-coding RNAs, the cellular function remains enigmatic. The two long non-coding RNA (lncRNA) genes DLEU1 and DLEU2 map to a critical region at chromosomal band 13q14.3 that is recurrently deleted in solid tumors and hematopoietic malignancies like chronic lymphocytic leukemia (CLL). While no point mutations have been found in the protein coding candidate genes at 13q14.3, they are deregulated in malignant cells, suggesting an epigenetic tumor suppressor mechanism. We therefore characterized the epigenetic makeup of 13q14.3 in CLL cells and found histone modifications by chromatin-immunoprecipitation (ChIP) that are associated with activated transcription and significant DNA-demethylation at the transcriptional start sites of DLEU1 and DLEU2 using 5 different semi-quantitative and quantitative methods (aPRIMES, BioCOBRA, MCIp, MassARRAY, and bisulfite sequencing). These epigenetic aberrations were correlated with transcriptional deregulation of the neighboring candidate tumor suppressor genes, suggesting a coregulation in cis of this gene cluster. We found that the 13q14.3 genes in addition to their previously known functions regulate NF-kB activity, which we could show after overexpression, siRNA-mediated knockdown, and dominant-negative mutant genes by using Western blots with previously undescribed antibodies, by a customized ELISA as well as by reporter assays. In addition, we performed an unbiased screen of 810 human miRNAs and identified the miR-15/16 family of genes at 13q14.3 as the strongest inducers of NF-kB activity. In summary, the tumor suppressor mechanism at 13q14.3 is a cluster of genes controlled by two lncRNA genes that are regulated by DNA-methylation and histone modifications and whose members all regulate NF-kB. Therefore, the tumor suppressor mechanism in 13q14.3 underlines the role both of epigenetic aberrations and of lncRNA genes in human tumorigenesis and is an example of colocalization of a functionally related gene cluster.
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