ArticleOncoTargets and therapy2016
p53 inhibits the expression of p125 and the methylation of POLD1 gene promoter by downregulating the Sp1-induced DNMT1 activities in breast cancer.
Article in OncoTargets and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Beyond proofreading: POLD1 mutations as dynamic orchestrators of genomic instability and immune evasion in cancer.Frontiers in immunology · 2025Review
- Targeting POLD1 to suppress the proliferation and migration of breast cancer MDA-MB-231 cell lines by downregulation of SIRT1.Toxicology research · 2024Article
- Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics.International journal of molecular sciences · 2023Article
- Prospects of POLD1 in Human Cancers: A Review.Cancers · 2023Review
- Identification of potential microRNA diagnostic panels and uncovering regulatory mechanisms in breast cancer pathogenesis.Scientific reports · 2022Article
- miR-195-3p alleviates homocysteine-mediated atherosclerosis by targeting IL-31 through its epigenetics modifications.Aging cell · 2021Article
- Development and validation of a novel metabolic signature for predicting prognosis in patients with laryngeal cancer.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Article
- Comprehensive analysis of regulation of DNA methyltransferase isoforms in human breast tumors.Journal of cancer research and clinical oncology · 2021Review
- Construction of a Potential Breast Cancer-Related miRNA-mRNA Regulatory Network.BioMed research international · 2020Article
- Elevated expression of POLD1 is associated with poor prognosis in breast cancer.Oncology letters · 2018Article
- Article
- GenePANDA-a novel network-based gene prioritizing tool for complex diseases.Scientific reports · 2017Article
- Casticin inhibits the activity of transcription factor Sp1 and the methylation ofExperimental and therapeutic medicine · 2017Article
- Targeting EP4 downstream c-Jun through ERK1/2-mediated reduction of DNMT1 reveals novel mechanism of solamargine-inhibited growth of lung cancer cells.Journal of cellular and molecular medicine · 2017Article
- MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion.Cell proliferation · 2016Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p125 is one of four subunits of human DNA polymerases - DNA Pol δ as well as one of p53 target protein encoded by POLD1. However, the function and significance of p125 and the role that p53 plays in regulating p125 expression are not fully understood in breast cancer. Tissue sections of human breast cancer obtained from 70 patients whose median age was 47.6 years (range: 38-69 years) with stage II-III breast cancer were studied with normal breast tissue from the same patients and two human breast cell lines (MCF-7 and MCF-10A). p53 expression levels were reduced, while p125 protein expression was increased in human breast cancer tissues and cell line detected by Western blot and quantitative reverse transcriptase-polymerase chain reaction. The methylation level of the POLD1 gene promoter was greater in breast cancer tissues and cells when compared with normal tissues and cells. In MCF-7 cell model, p53 overexpression caused a decrease in the level of p125 protein, while the methylation level of the p125 gene promoter was also inhibited by p53 overexpression. To further investigate the regulating mechanism of p53 on p125 expression, our study focused on DNA methyltransferase 1 (DNMT1) and transcription factor Sp1. Both DNMT1 and Sp1 protein expression were reduced when p53 was overexpressed in MCF-7 cells. The Sp1 binding site appears to be important for DNMT1 gene transcription; Sp1 and p53 can bind together, which means that DNMT1 gene expression may be downregulated by p53 through binding to Sp1. Because DNMT1 methylation level of the p125 gene promoter can affect p125 gene transcription, we propose that p53 may indirectly regulate p125 gene promoter expression through the control of DNMT1 gene transcription. In conclusion, the data from this preliminary study have shown that p53 inhibits the methylation of p125 gene promoter by downregulating the activities of Sp1 and DNMT1 in breast cancer.
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