ArticlePloS one2013
Epigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Epigenetic regulation and factors that influence the effect of iPSCs-derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury.Clinical epigenetics · 2024Review
- KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024Review
- Profiling of Circulating Tumor Cells for Screening of Selective Inhibitors of Tumor-Initiating Stem-Like Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- Fermented Ginseng Extract, BST204, Suppresses Tumorigenesis and Migration of Embryonic Carcinoma through Inhibition of Cancer Stem Cell Properties.Molecules (Basel, Switzerland) · 2020Article
- Research Progress in Liver-Regenerating Microenvironment and DNA Methylation in Hepatocellular Carcinoma: The Role of Traditional Chinese Medicine.Medical science monitor : international medical journal of experimental and clinical research · 2020Review
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Niche Modulation of IGF-1R Signaling: Its Role in Stem Cell Pluripotency, Cancer Reprogramming, and Therapeutic Applications.Frontiers in cell and developmental biology · 2020Review
- Genome-wide promoter DNA methylation profiling of hepatocellular carcinomas arising either spontaneously or due to chronic exposure to Ginkgo biloba extract (GBE) in B6C3F1/N mice.Archives of toxicology · 2019Article
- Oct3/4 is potentially useful for the suppression of the proliferation and motility of hepatocellular carcinoma cells.Oncology letters · 2018Article
- Article
- Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells.Molecules (Basel, Switzerland) · 2017Article
- Accumulation of low-dose BIX01294 promotes metastatic potential of U251 glioblastoma cells.Oncology letters · 2017Article
- Oxidative stress-induced epigenetic changes associated with malignant transformation of human kidney epithelial cells.Oncotarget · 2017Article
- Article
- CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency.Cell death and differentiation · 2017Article
- Stemness-related transcriptional factors and homing gene expression profiles in hepatic differentiation and cancer.Molecular medicine (Cambridge, Mass.) · 2016Article
- In vivo epigenetic reprogramming of primary human colon cancer cells enhances metastases.Journal of molecular cell biology · 2016Article
- Modified Nucleotides for Discrimination between Cytosine and the Epigenetic Marker 5-Methylcytosine.Angewandte Chemie (International ed. in English) · 2016Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+(high) cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+(high) cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression.
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