ArticlePloS one2012
Loss of imprinting and allelic switching at the DLK1-MEG3 locus in human hepatocellular carcinoma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Emerging Roles of p53 Related lncRNAs in Cancer Progression: A Systematic Review.International journal of biological sciences · 2019Pooled it
- EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.Cell death & disease · 2014Trial
- Putative Imprinting Control Regions with Aberrant Blood-Based DNA Methylation are Associated with Hepatocellular Carcinoma Risk.Journal of hepatocellular carcinoma · 2026Article
- Navigating liver cancer: Precision targeting for enhanced treatment outcomes.Drug delivery and translational research · 2025Review
- Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.Clinical epigenetics · 2025Article
- HCC-Related lncRNAs: Roles and Mechanisms.International journal of molecular sciences · 2024Review
- The role of imprinting genes' loss of imprints in cancers and their clinical implications.Frontiers in oncology · 2024Review
- 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
- Serum non-coding RNAs for diagnosis and stage of liver fibrosis.Journal of clinical laboratory analysis · 2022Review
- lncRNA MEG3 modulates hepatic stellate cell activation by sponging miR‑145 to regulate PPARγ.Molecular medicine reports · 2022Article
- A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers.Frontiers in cell and developmental biology · 2022Review
- Emerging role of long noncoding RNAs in recurrent hepatocellular carcinoma.World journal of clinical cases · 2021Review
- The long and the small collide: LncRNAs and small heterodimer partner (SHP) in liver disease.Molecular and cellular endocrinology · 2021Review
- Review
- Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines.Clinical epigenetics · 2021Article
- The Roles and Mechanisms of lncRNAs in Liver Fibrosis.Frontiers in pharmacology · 2021Review
- LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma.International journal of molecular sciences · 2020Review
- Predicting miRNA targets for hepatocellular carcinoma with an integrated method.Translational cancer research · 2020Article
- The effects of long non-coding ribonucleic acids on various cellular components in rheumatoid arthritis.Rheumatology (Oxford, England) · 2020Review
- Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies.Frontiers in medicine · 2020Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulation of imprinted genes is an important molecular mechanism contributing to the development of cancer in humans. However, knowledge about imprinting defects in human hepatocellular carcinoma (HCC), the third leading cause of cancer mortality worldwide, is still limited. Therefore, a systematic meta-analysis of the expression of 223 imprinted loci in human HCC was initiated. This screen revealed that the DLK1-MEG3 locus is frequently deregulated in HCC. Deregulation of DLK1 and MEG3 expression accompanied by extensive aberrations in DNA methylation could be confirmed experimentally in an independent series of human HCC (n = 40) in more than 80% of cases. Loss of methylation at the DLK1-MEG3 locus correlates linearly with global loss of DNA methylation in HCC (r(2) = 0.63, p<0.0001). Inhibition of DNMT1 in HCC cells using siRNA led to a reduction in MEG3-DMR methylation and concomitant increase in MEG3 RNA expression. Allele-specific expression analysis identified loss of imprinting in 10 out of 31 informative samples (32%), rendering it one of the most frequent molecular defects in human HCC. In 2 cases unequivocal gain of bi-allelic expression accompanied by substantial loss of methylation at the IG-DMR could be demonstrated. In 8 cases the tumour cells displayed allelic switching by mono-allelic expression of the normally imprinted allele. Allelic switching was accompanied by gains or losses of DNA methylation primarily at IG-DMR1. Analysis of 10 hepatocellular adenomas (HCA) and 5 cases of focal nodular hyperplasia (FNH) confirmed that this epigenetic instability is specifically associated with the process of malignant transformation and not linked to increased proliferation per se. This widespread imprint instability in human HCC has to be considered in order to minimize unwanted side-effects of therapeutic approaches targeting the DNA methylation machinery. It might also serve in the future as predictive biomarker and for monitoring response to epigenetic therapy.
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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.