ArticleThe Journal of biological chemistry2011
DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed.
- Ancestry informative genetic variants associated with tobacco metabolic and detoxification capacity measured by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) among smokers.Archives of toxicology · 2026Article
- DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma.Translational oncology · 2024Article
- DLK1/DIO3 locus upregulation by a β-catenin-dependent enhancer drives cell proliferation and liver tumorigenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- AAV-based gene therapy ameliorated CNS-specific GPI defect in mouse models.Molecular therapy. Methods & clinical development · 2024Article
- Review
- MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- miR-134-3p driven by anisomycin impairs ovarian cancer stem cell activity through inhibiting GPR137 expression.Journal of Cancer · 2023Article
- Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog interacting protein.BMC gastroenterology · 2022Article
- Pituitary Tumor-Transforming Gene 1/Delta like Non-Canonical Notch Ligand 1 Signaling in Chronic Liver Diseases.International journal of molecular sciences · 2022Review
- Article
- Molecular classification of hepatocellular carcinoma: prognostic importance and clinical applications.Journal of cancer research and clinical oncology · 2022Review
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- Neonatal Exposure to BPA, BDE-99, and PCB Produces Persistent Changes in Hepatic Transcriptome Associated With Gut Dysbiosis in Adult Mouse Livers.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Hepatic Cancer Stem Cells: Molecular Mechanisms, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2021Review
- Low incidence of hepatocellular carcinoma in mice and cats treated with systemic adeno-associated viral vectors.Molecular therapy. Methods & clinical development · 2021Article
- Article
- Elucidating the Molecular Basis of Sorafenib Resistance in HCC: Current Findings and Future Directions.Journal of hepatocellular carcinoma · 2021Review
- Omics-Based Identification of Shared and Gender Disparity Routes inFrontiers in genetics · 2021Article
- Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study.Frontiers of medicine · 2020Article
25 more citing papers are in PubMed but not listed here.
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18 authors.
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Abstract
Hepatocellular carcinoma (HCC) is a heterogeneous and highly aggressive malignancy, for which there are no effective cures. Identification of a malignant stemlike subtype of HCC may offer patients with a dismal prognosis a potential targeted therapy using c-MET and Wnt pathway inhibitors. MicroRNAs (miRNAs) show promise as diagnostic and prognostic tools for cancer detection and stratification. Using a TRE-c-Met-driven transgenic HCC mouse model, we identified a cluster of 23 miRNAs that is encoded within the Dlk1-Gtl2 imprinted region on chromosome 12qF1 overexpressed in all of the isolated liver tumors. Interestingly, this region is conserved among mammalian species and maps to the human DLK1-DIO3 region on chromosome 14q32.2. We thus examined the expression of the DLK1-DIO3 miRNA cluster in a cohort of 97 hepatitis B virus-associated HCC patients and identified a subgroup (n = 18) of patients showing strong coordinate overexpression of miRNAs in this cluster but not in other cancer types (breast, lung, kidney, stomach, and colon) that were tested. Expression levels of imprinted gene transcripts from neighboring loci in this 14q32.2 region and from a subset of other imprinted sites were concomitantly elevated in human HCC. Interestingly, overexpression of the DLK1-DIO3 miRNA cluster was positively correlated with HCC stem cell markers (CD133, CD90, EpCAM, Nestin) and associated with a high level of serum α-fetoprotein, a conventional biomarker for liver cancer, and poor survival rate in HCC patients. In conclusion, our findings suggest that coordinate up-regulation of the DLK1-DIO3 miRNA cluster at 14q32.2 may define a novel molecular (stem cell-like) subtype of HCC associated with poor prognosis.
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