ArticleClinical epigenetics2019
UHRF1 depletion and HDAC inhibition reactivate epigenetically silenced genes in colorectal cancer cells.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- A Hybrid compound H93 treats prostate cancer by directly binding UHRF1 and promoting protein dimerization.Communications chemistry · 2025Article
- Novel insights into lncRNAs as key regulators of post-translational modifications in cancer: mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells.EMBO molecular medicine · 2024Article
- Oncogenic Roles of UHRF1 in Cancer.Epigenomes · 2024Review
- DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.Exploration of targeted anti-tumor therapy · 2024Review
- Mechanistic insights into UHRF1‑mediated DNA methylation by structure‑based functional clarification of UHRF1 domains (Review).Oncology letters · 2023Review
- Downregulation of DNA methylation enhances differentiation of THP-1 cells and induces M1 polarization of differentiated macrophages.Scientific reports · 2023Article
- Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation.JCI insight · 2022Article
- Characterization of RNF43 frameshift mutations that drive Wnt ligand- and R-spondin-dependent colon cancer.The Journal of pathology · 2022Article
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- Crosstalk between macrophage-derived PGETheranostics · 2022Article
- DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes.Scientific reports · 2021Article
- NBM-BMX, an HDAC8 Inhibitor, Overcomes Temozolomide Resistance in Glioblastoma Multiforme by Downregulating the β-Catenin/c-Myc/SOX2 Pathway and Upregulating p53-Mediated MGMT Inhibition.International journal of molecular sciences · 2021Article
- Review
- Zinc Metalloproteins in Epigenetics and Their Crosstalk.Life (Basel, Switzerland) · 2021Review
- UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUbiquitin-like protein containing PHD and RING finger domains 1 (UHRF1) is a major regulator of epigenetic mechanisms and is overexpressed in various human malignancies. In this study, we examined the involvement of UHRF1 in aberrant DNA methylation and gene silencing in colorectal cancer (CRC).
resultsCRC cell lines were transiently transfected with siRNAs targeting UHRF1, after which DNA methylation was analyzed using dot blots, bisulfite pyrosequencing, and Infinium HumanMethylation450 BeadChip assays. Gene expression was analyzed using RT-PCR and gene expression microarrays. Depletion of UHRF1 rapidly induced genome-wide DNA demethylation in CRC cells. Infinium BeadChip assays and bisulfite pyrosequencing revealed significant demethylation across entire genomic regions, including CpG islands, gene bodies, intergenic regions, and repetitive elements. Despite the substantial demethylation, however, UHRF1 depletion only minimally reversed CpG island hypermethylation-associated gene silencing. By contrast, the combination of UHRF1 depletion and histone deacetylase (HDAC) inhibition reactivated the silenced genes and strongly suppressed CRC cell proliferation. The combination of UHRF1 depletion and HDAC inhibition also induced marked changes in the gene expression profiles such that cell cycle-related genes were strikingly downregulated.
conclusionsOur results suggest that (i) maintenance of DNA methylation in CRC cells is highly dependent on UHRF1; (ii) UHRF1 depletion rapidly induces DNA demethylation, though it is insufficient to fully reactivate the silenced genes; and (iii) dual targeting of UHRF1 and HDAC may be an effective new therapeutic strategy.
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