ArticleJournal of hematology & oncology2017
Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 99 citations in OpenAlex.
- DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells.Clinical epigenetics · 2025Article
- 5'-Methylthioadenosine Metabolic Reprogramming Drives H3K79 Monomethylation-Mediated PAK2 Upregulation to Promote Cadmium-Induced Breast Cancer Progression by Impairing Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma.Cancer medicine · 2024Article
- DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1.Cell communication and signaling : CCS · 2024Article
- Dexamethasone Inhibits the Growth of B-Lymphoma Cells by Downregulating DOT1L.Cancer reports (Hoboken, N.J.) · 2024Article
- Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer.Acta pharmaceutica Sinica. B · 2024Article
- Nucleophosmin 1 cooperates with the methyltransferase DOT1L to preserve peri-nucleolar heterochromatin organization by regulating H3K27me3 levels and DNA repeats expression.Epigenetics & chromatin · 2023Article
- DOT1 L Regulates Ovarian Cancer Stem Cells by Activating β-catenin Signaling.Molecular cancer research : MCR · 2023Article
- DOT1L promotes cell proliferation and invasion by epigenetically regulating STAT5B in renal cell carcinoma.American journal of cancer research · 2023Article
- Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome.Frontiers in cell and developmental biology · 2023Article
- Combinatorial targeting of menin and the histone methyltransferase DOT1L as a novel therapeutic strategy for treatment of chemotherapy-resistant ovarian cancer.Cancer cell international · 2022Article
- The senescence-associated secretory phenotype in ovarian cancer dissemination.American journal of physiology. Cell physiology · 2022Review
- Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.Frontiers in genetics · 2022Review
- Insights Into the Role of Epigenetic Factors Determining the Estrogen Response in Estrogen-Positive Ovarian Cancer and Prospects of Combining Epi-Drugs With Endocrine Therapy.Frontiers in genetics · 2022Review
- Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons.Nature neuroscience · 2021Article
- Histone Modifying Enzymes in Gynaecological Cancers.Cancers · 2021Review
- Research Progress in Prognostic Factors and Biomarkers of Ovarian Cancer.Journal of Cancer · 2021Review
- The Prognostic Value of the DNA Repair Gene Signature in Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective ofCancers · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpigenetics has been known to play a critical role in regulating the malignant phenotype. This study was designed to examine the expression of DOT1L (histone 3 lysine 79 methyltransferase) and H3K79 methylation in normal ovarian tissues and ovarian tumors and to explore the function of DOT1L and its underline mechanisms in ovarian cancer.
methodsThe expression of DOT1L and H3K79 methylation in 250 ovarian tumor samples and 24 normal ovarian samples was assessed by immunohistochemistry. The effects of DOT1L on cell proliferation in vitro were evaluated using CCK8, colony formation and flow cytometry. The DOT1L-targeted genes were determined using chromatin immune-precipitation coupled with high-throughput sequencing (ChIP-seq) and ChIP-PCR. Gene expression levels were measured by real-time PCR and immunoblotting. The effects of DOT1L on tumor growth in vivo were evaluated using an orthotopic ovarian tumor model.
resultsDOT1L expression and H3K79 methylation was significantly increased in malignant ovarian tumors. High DOT1L expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade, and lymphatic metastasis. DOT1L was an independent prognostic factor for the overall survival (OS) and progression-free survival (PFS) of ovarian cancer, and higher DOT1L expression was associated with poorer OS and PFS. Furthermore, DOT1L regulates the transcription of G1 phase genes CDK6 and CCND3 through H3K79 dimethylation; therefore, blocking DOT1L could result in G1 arrest and thereby impede the cell proliferation in vitro and tumor growth in vivo.
conclusionsOur findings first demonstrate that DOT1L over-expression has important clinical significance in ovarian cancer and also clarify that it drives cell cycle progression through transcriptional regulation of CDK6 and CCND3 through H3K79 methylation, suggesting that DOT1L might be potential target for prognostic assessment and therapeutic intervention in ovarian cancer.
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