Insights into DNMT1 and programmed cell death in diseases

Yan, Lan; Geng, Qi; Cao, Zhiwen; Liu, Bin; Li, Li; Lu, Peipei; Lin, Lin; Wei, Lini; Tan, Yong; He, Xiaojuan; Li, Li; Zhao, Ning; Lu, Cheng

doi:10.1016/j.biopha.2023.115753

Cited by 9 publications

(1 citation statement)

References 161 publications

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“…In mammalian cells, DNMTs can be classified into three main types: DNMT1, DNMT3a, and DNMT3b. DNMT1 is responsible for maintaining the existing DNA methylation state, as well as catalyzing hemimethylated DNA and participating in DNA methylation repair (Yan et al, 2023). On the other hand, DNMT3a and DNMT3b catalyze the addition of new methyl groups to unmethylated DNA, converting it into methylated DNA (Lyko, 2018).…”

Section: Dna Methylationmentioning

confidence: 99%

Research progress and applications of epigenetic biomarkers in cancer

Gao,

Shi,

Wang

et al. 2024

Front. Pharmacol.

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Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.

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Section: Dna Methylationmentioning

confidence: 99%

Research progress and applications of epigenetic biomarkers in cancer

Gao,

Shi,

Wang

et al. 2024

Front. Pharmacol.

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DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy

Li,

Guo,

Zhang

et al. 2024

Mol Biol Rep

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Background Acute myeloid leukemia (AML) is a common hematological tumor, but it is difficult to treat. DNMT1 is a DNA methyltransferase whose main function is to maintain stable DNA methylation during the DNA replication process. DNMT1 also plays an important role in AML, but its function in cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear. Methods and results In this study, we isolated primary NK cells from the peripheral blood of healthy volunteers and AML patients and treated them with 10 ng/mL IL-12, 50 ng/mL IL-15 and 50 ng/mL IL-18 to promote their differentiation into CIML NK cells. The activity of CIML NK cells was evaluated by RT‒qPCR, western blotting, ELISAs, and flow cytometry. DNMT1 was highly expressed in NK cells from AML patients. Knocking down DNMT1 significantly increased the expression of CD25, CD137, CD107a, IFN-γ, and TNF-α and increased the activity of CIML NK cells. Mechanistically, knocking down DNMT1 promoted autophagy by activating the AMPK/mTOR signaling pathway, thereby enhancing the activity of CIML NK cells and alleviating the progression of AML. Conclusions Our study revealed that the downregulation of DNMT expression may be a new target for the treatment of AML. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-024-10181-9.

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Enhancing antitumor activity of herceptin in HER2-positive breast cancer cells: a novel DNMT-1 inhibitor approach

Ren,

Song,

Song

et al. 2024

Discov Onc

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HER2 antagonists remain the cornerstone of therapy for patients with HER2-positive breast cancer. This study introduces a novel small-molecule inhibitor of DNA methyltransferase 1 (DNMT-1), referred to as DI-1, designed to synergize with HER2 antagonists in treating HER2-positive breast cancer cells. Clinical data reveal a negative correlation between DNMT-1 expression and PTEN levels, and a positive correlation with the methylation rates of PTEN's promoter. In experiments with SKBR3 and BT474 cells, DI-1 effectively reduced the methylation of PTEN's promoter region, thereby upregulating PTEN expression. This upregulation, in turn, enhanced the cells' sensitivity to HER2 antagonists, indicating that DI-1’s mechanism involves inhibiting DNMT-1’s recruitment to PTEN's promoter region. Consequently, by increasing PTEN expression, DI-1 amplifies the sensitivity of HER2-positive breast cancer cells to treatment, suggesting its potential as a promising therapeutic strategy in this context. Supplementary Information The online version contains supplementary material available at 10.1007/s12672-024-01508-w.

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Insights into DNMT1 and programmed cell death in diseases

Cited by 9 publications

References 161 publications

Research progress and applications of epigenetic biomarkers in cancer

Research progress and applications of epigenetic biomarkers in cancer

DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy

Enhancing antitumor activity of herceptin in HER2-positive breast cancer cells: a novel DNMT-1 inhibitor approach

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