ArticleBlood2008
Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemia.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed.
- Randomized trial of 10 days of decitabine ± bortezomib in untreated older patients with AML: CALGB 11002 (Alliance).Blood advances · 2018Trial
- An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes.American journal of hematology · 2017Trial
- Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia.Blood · 2012Trial
- Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy.Haematologica · 2011Trial
- Regulatory function of ten‑eleven translocation‑2 in transcriptional mechanisms of demethylated myeloma cells.Molecular medicine reports · 2026Article
- RNA methylation in cell death: mechanisms and clinical applications.Molecular cancer · 2026Review
- Article
- A Comprehensive Guide on Epigenetics' Precision Role in Uncommon "Rare" Cancers' Biology and Treatment Frontiers.Sub-cellular biochemistry · 2026Review
- Article
- Functions, mechanisms, and therapeutic implications of noncoding RNA in acute myeloid leukemia.Fundamental research · 2025Review
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- The Bidirectional Interaction Between NF-Journal of immunology research · 2025Review
- Synthetic Curcumin Analogs in the Treatment of Cancer: A Literature Review.Current medicinal chemistry · 2025Review
- Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach.The EPMA journal · 2024Article
- Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress.Journal of cellular and molecular medicine · 2024Article
- Review
- 5-Aza-2'-Deoxycytidine Alters the Methylation Profile of Bortezomib-Resistant U266 Multiple Myeloma Cells and Affects Their Proliferative Potential.International journal of molecular sciences · 2023Article
- In situ Electrochemical Evaluation of the Interaction of dsDNA with the Proteasome Inhibitor Anticancer Drug Bortezomib.Molecules (Basel, Switzerland) · 2023Article
- Review
- DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation.Annals of medicine · 2022Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
Bortezomib reversibly inhibits 26S proteasomal degradation, interferes with NF-kappaB, and exhibits antitumor activity in human malignancies. Zinc finger protein Sp1 transactivates DNMT1 gene in mice and is functionally regulated through protein abundance, posttranslational modifications (ie, ubiquitination), or interaction with other transcription factors (ie, NF-kappaB). We hypothesize that inhibition of proteasomal degradation and Sp1/NF-kappaB-mediated transactivation may impair aberrant DNA methyltransferase activity. We show here that, in addition to inducing accumulation of polyubiquitinated proteins and abolishment of NF-kappaB activities, bortezomib decreases Sp1 protein levels, disrupts the physical interaction of Sp1/NF-kappaB, and prevents binding of the Sp1/NF-kappaB complex to the DNMT1 gene promoter. Abrogation of Sp1/NF-kappaB complex by bortezomib causes transcriptional repression of DNMT1 gene and down-regulation of DNMT1 protein, which in turn induces global DNA hypomethylation in vitro and in vivo and re-expression of epigenetically silenced genes in human cancer cells. The involvement of Sp1/NF-kappaB in DNMT1 regulation is further demonstrated by the observation that Sp1 knockdown using mithramycin A or shRNA decreases DNMT1 protein levels, which instead are increased by Sp1 or NF-kappaB overexpression. Our results unveil the Sp1/NF-kappaB pathway as a modulator of DNA methyltransferase activity in human cancer and identify bortezomib as a novel epigenetic-targeting drug.
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Registered trials
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.