ArticleOncology letters2018
Histone deacetylase inhibitors induce the expression of tumor suppressor genes Per1 and Per2 in human gastric cancer cells.
Article in Oncology letters, 2018. 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, 28 citations in OpenAlex.
- Circadian clock and cancer.Military Medical Research · 2026Review
- Decoding Multifaceted Roles of Sleep-Related Genes as Molecular Bridges in Chronic Disease Pathogenesis.International journal of molecular sciences · 2025Review
- Bidirectional crosstalk between sleep disorders and gynecological cancers: unraveling molecular synergies and precision therapeutics.Frontiers in medicine · 2025Review
- PER1 Serves as a Tumor Suppressor in Breast Cancer by Regulating MEK5/ERK5 Signaling Pathway.International journal of general medicine · 2025Article
- Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.Journal of gastrointestinal cancer · 2024Article
- Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c.Cancer gene therapy · 2023Article
- Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy?Frontiers in immunology · 2023Review
- Characterization of SN38-resistant T47D breast cancer cell sublines overexpressing BCRP, MRP1, MRP2, MRP3, and MRP4.BMC cancer · 2022Article
- Development and performance evaluation of TaqMan real-time fluorescence quantitative methylation specific PCR for detecting methylation level of PER2.Molecular biology reports · 2022Article
- Small RNA perspective of physical exercise-related improvement of male reproductive dysfunction due to obesity.Frontiers in endocrinology · 2022Article
- Article
- PER1 as a Tumor Suppressor Attenuated in the Malignant Phenotypes of Breast Cancer Cells.International journal of general medicine · 2021Article
- The circadian rhythm and core gene Period2 regulate the chemotherapy effect and multidrug resistance of ovarian cancer through the PI3K signaling pathway.Bioscience reports · 2020Article
- Epigenetic Mechanisms in Gastric Cancer: Potential New Therapeutic Opportunities.International journal of molecular sciences · 2020Review
- Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Period circadian regulator (Per)1 and Per2 genes are involved in the molecular mechanism of the circadian clock, and exhibit tumor suppressor properties. Several studies have reported a decreased expression of Per1, Per2 and Per3 genes in different types of cancer and cancer cell lines. Promoter methylation downregulates Per1, Per2 or Per3 expression in myeloid leukemia, breast, lung, and other cancer cells; whereas histone deacetylase inhibitors (HDACi) upregulate Per1 or Per3 expression in certain cancer cell lines. However, the transcriptional regulation of Per1 and Per2 in cancer cells by chromatin modifications is not fully understood. The present study aimed to determine whether HDACi regulate Per1 and Per2 expression in gastric cancer cell lines, and to investigate changes in chromatin modifications in response to HDACi. Treatment of KATO III and NCI-N87 human gastric cancer cells with sodium butyrate (NaB) or Trichostatin A (TSA) induced Per1 and Per2 mRNA expression in a dose-dependent manner. Chromatin immunoprecipitaion assays revealed that NaB and TSA decreased lysine 9 trimethylation on histone H3 (H3K9me3) at the Per1 promoter. TSA, but not NaB increased H3K9 acetylation at the Per2 promoter. It was also observed that binding of Sp1 and Sp3 to the Per1 promoter decreased following NaB treatment, whereas Sp1 binding increased at the Per2 promoter of NaB- and TSA-treated cells. In addition, Per1 promoter is not methylated in KATO III cells, while Per2 promoter was methylated, although NaB, TSA, and 5-Azacytidine do not change the methylated CpGs analyzed. In conclusion, HDACi induce Per1 and Per2 expression, in part, through mechanisms involving chromatin remodeling at the proximal promoter of these genes; however, other indirect mechanisms triggered by these HDACi cannot be ruled out. These findings reveal a previously unappreciated regulatory pathway between silencing of Per1 gene by H3K9me3 and upregulation of Per2 by HDACi in cancer cells.
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