ArticleBioscience reports2020
The role of DOT1L in the proliferation and prognosis of gastric cancer.
Article in Bioscience reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- DOT1L as a Therapeutic Target: Insights into Epigenetic Regulation and Cancer Treatment.Biomolecules & therapeutics · 2025Review
- The anticancer potential of Origanum onites L. in gastric cancer through epigenetic alterations.BMC complementary medicine and therapies · 2025Article
- Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs.RSC medicinal chemistry · 2025Article
- Unraveling the role of long non-coding RNAs in therapeutic resistance in acute myeloid leukemia: New prospects & challenges.Non-coding RNA research · 2024Review
- 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
- The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.Histology and histopathology · 2024Review
- [PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Review
- The Role of Histone Modification in DNA Replication-Coupled Nucleosome Assembly and Cancer.International journal of molecular sciences · 2023Review
- Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome.Frontiers in cell and developmental biology · 2023Article
- Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis.Experimental & molecular medicine · 2023Review
- DOT1L promotes cell proliferation and invasion by epigenetically regulating STAT5B in renal cell carcinoma.American journal of cancer research · 2023Article
- Article
- Identification of Enhancer RNA CDK6-AS1 as a Potential Novel Prognostic Biomarker in Gastric Cancer.Frontiers in genetics · 2022Article
- Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.Frontiers in genetics · 2022Review
- Transcriptomic and ChIP-seq Integrative Analysis Identifies KDM5A-Target Genes in Cardiac Fibroblasts.Frontiers in cardiovascular medicine · 2022Article
- Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein.Molecules (Basel, Switzerland) · 2021Article
- DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A.The Journal of cell biology · 2021Article
- Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis.Oncogenesis · 2021Article
- Mutational Characterization and Potential Prognostic Biomarkers of Chinese Patients with Esophageal Squamous Cell Carcinoma.OncoTargets and therapy · 2020Article
Corrections and comments
- Expression of concern
- Retracted
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDisruptor of telomeric silencing-1-like (DOT1L), a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer (GC) and healthy samples.
methodsImmunohistochemistry was used to detect DOT1L levels in 101 cases of GC and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by cell counting kit-8 (CCK-8) and clone formation assays, with flow cytometry for observing the cell cycle. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model.
resultsThe expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates cyclin-dependent kinase (CDK) 4 (CDK4) and CDK6 through H3K79me2, which leads to a change in the cell cycle at G1, thereby affecting the proliferation of tumors in vitro and in vivo.
conclusionsThis is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of GC.
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