ArticleClinical epigenetics2014
Concomitant downregulation of the imprinted genes DLK1 and MEG3 at 14q32.2 by epigenetic mechanisms in urothelial carcinoma.
Article in Clinical epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.Clinical epigenetics · 2025Article
- Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines.Clinical epigenetics · 2022Article
- A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers.Frontiers in cell and developmental biology · 2022Review
- Review
- LncRNAInternational journal of molecular sciences · 2021Article
- Dysregulation of ncRNAs located at the DLK1‑DIO3 imprinted domain: involvement in urological cancers.Cancer management and research · 2019Review
- Structural characterization of maternally expressed gene 3 RNA reveals conserved motifs and potential sites of interaction with polycomb repressive complex 2.Nucleic acids research · 2018Article
- Identification of miR-379/miR-656 (C14MC) cluster downregulation and associated epigenetic and transcription regulatory mechanism in oligodendrogliomas.Journal of neuro-oncology · 2018Article
- Long non-coding RNA expression in bladder cancer.Biophysical reviews · 2018Review
- MEG3 inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells.Oncology letters · 2018Article
- The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5.Frontiers in pharmacology · 2018Article
- Comprehensive analysis of mRNA-lncRNA co-expression profile revealing crucial role of imprinted gene cluster DLK1-MEG3 in chordoma.Oncotarget · 2017Article
- Review
- Potential applications of MEG3 in cancer diagnosis and prognosis.Oncotarget · 2017Review
- Article
- Low maternal adherence to a Mediterranean diet is associated with increase in methylation at theEnvironmental epigenetics · 2017Article
- Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.PloS one · 2017Article
- Identification of a serum circulating lncRNA panel for the diagnosis and recurrence prediction of bladder cancer.Oncotarget · 2016Article
- Effect on Multipotency and Phenotypic Transition of Unrestricted Somatic Stem Cells from Human Umbilical Cord Blood after Treatment with Epigenetic Agents.Stem cells international · 2016Article
- Long Non-coding RNAs in Urologic Malignancies: Functional Roles and Clinical Translation.Journal of Cancer · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe two oppositely imprinted and expressed genes, DLK1 and MEG3, are located in the same gene cluster at 14q32. Previous studies in bladder cancer have suggested that tumor suppressor genes are located in this region, but these have not been identified.
resultsWe observed that both DLK1 and MEG3 are frequently silenced in urothelial cancer tissues and cell lines. The concomitant downregulation of the two genes is difficult to explain by known mechanisms for inactivating imprinted genes, namely deletion of active alleles or epitype switching. Indeed, quantitative PCR revealed more frequent copy number gains than losses in the gene cluster that were, moreover, consistent within each sample, excluding gene losses as the cause of downregulation. Instead, we observed distinctive epigenetic alterations at the three regions controlling DLK1 and MEG3 expression, namely the DLK1 promoter; the intergenic (IG) and MEG3 differentially methylated regions (DMRs). Bisulfite sequencing and pyrosequencing revealed novel patterns of DNA methylation in tumor cells, which were distinct from that of either paternal allele. Furthermore, chromatin immunoprecipitation demonstrated loss of active and gain of repressive histone modifications at all regulatory sequences.
conclusionsOur data support the idea that the main cause of the prevalent downregulation of DLK1 and MEG3 in urothelial carcinoma is epigenetic silencing across the 14q32 imprinted gene cluster, resulting in the unusual concomitant inactivation of oppositely expressed and imprinted genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.