ArticleScientific reports2015
Five-aza-2'-deoxycytidine-induced hypomethylation of cholesterol 25-hydroxylase gene is responsible for cell death of myelodysplasia/leukemia cells.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The Coming of Age of Preclinical Models of MDS.Frontiers in oncology · 2022Pooled it
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.Frontiers in cellular and infection microbiology · 2026Review
- TP-0903 Suppresses Aurora A-PLK1 Signaling to Inhibit Proliferation of a Myelodysplastic Syndrome-Derived Cell Line.Cancer science · 2025Article
- Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.The EMBO journal · 2024Article
- Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells.Molecular cancer research : MCR · 2023Article
- Role of reactive oxygen species in regulating 27-hydroxycholesterol-induced apoptosis of hematopoietic progenitor cells and myeloid cell lines.Cell death & disease · 2022Article
- Article
- Silylation of Deoxynucleotide Analog Yields an Orally Available Drug with Antileukemia Effects.Molecular cancer therapeutics · 2021Article
- Recurrence-Associated Multi-RNA Signature to Predict Disease-Free Survival for Ovarian Cancer Patients.BioMed research international · 2020Article
- The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis.Journal of Crohn's & colitis · 2019Article
- The augmented expression of the cytidine deaminase gene by 5-azacytidine predicts therapeutic efficacy in myelodysplastic syndromes.Oncotarget · 2019Article
- The Roles of Cholesterol and Its Metabolites in Normal and Malignant Hematopoiesis.Frontiers in endocrinology · 2019Review
- KIF20A, highly expressed in immature hematopoietic cells, supports the growth of HL60 cell line.International journal of hematology · 2018Article
- An MDS-derived cell line and a series of its sublines serve as an in vitro model for the leukemic evolution of MDS.Leukemia · 2018Article
- Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer.Journal of biomedical science · 2018Review
- Chromatin Regulation by HP1γ Contributes to Survival of 5-Azacytidine-Resistant Cells.Frontiers in pharmacology · 2018Article
- Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review).International journal of oncology · 2016Review
- Withaferin A suppresses the growth of myelodysplasia and leukemia cell lines by inhibiting cell cycle progression.Cancer science · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methyltransferase inhibitors (DNMT inhibitors) are administered for high-risk MDS, but their action mechanisms are not fully understood. Hence, we performed a genome-wide DNA methylation assay and focused on cholesterol 25-hydroxylase (CH25H) among the genes whose expression was up-regulated and whose promoter region was hypomethylated after decitabine (DAC) treatment in vitro. CH25H catalyzes hydroxylation of cholesterol and produces 25-hydroxycholesterol (25-OHC). Although CH25H mRNA expression level was originally low in MDS/leukemia cell lines, exposure to DNMT inhibitors enhanced CH25H mRNA expression. The promoter region of CH25H was originally hypermethylated in HL-60 and MDS-L cells, but DAC treatment induced their hypomethylation together with increased CH25H mRNA expression, activation of CH25H-oxysterol pathway, 25-OHC production and apoptotic cell death. We further confirmed that normal CD34-positive cells revealed hypomethylated status of the promoter region of CH25H gene. CH25H-knockdown by transfection of shRNA lentiviral vector into the cell lines partially protected the cells from DAC-induced cell death. Exogenous addition of 25-OHC suppressed leukemic cell growth. The present study raises a possibility that DNMT inhibitors activate CH25H-oxysterol pathway by their hypomethylating mechanism and induce leukemic cell death. Further investigations of the promoter analysis of CH25H gene and therapeutic effects of DNMT inhibitors on MDS/leukemia will be warranted.
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