ArticleOncology reports2019
Crosstalk between histone modification and DNA methylation orchestrates the epigenetic regulation of the costimulatory factors, Tim‑3 and galectin‑9, in cervical cancer.
Article in Oncology reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- A novel epigenetic regulation of JAM-A by EZH2-DNMT3A cascade contributes to T cell adhesion via the activation of Rap1a in lupus patients.Journal of translational autoimmunity · 2026Article
- Reprogramming the tumor immune microenvironment in cervical cancer: synergy between radiotherapy and immunotherapy.Molecular cancer · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Review
- DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review.International journal of molecular sciences · 2025Review
- Histone modifications in cervical cancer: Epigenetic mechanisms, functions and clinical implications (Review).Oncology reports · 2025Review
- Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.Cancer innovation · 2025Review
- Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.Journal of experimental & clinical cancer research : CR · 2025Review
- Epigenetic Biomarkers for Cervical Cancer Progression: A Scoping Review.International journal of molecular sciences · 2025Article
- Review
- Exogenous Galectin-9 prevents peri-implantitis in rats by regulating macrophage polarization.Frontiers in pharmacology · 2025Article
- Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis.Infectious agents and cancer · 2024Review
- Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.Blood cancer journal · 2024Article
- EZH2-Myc Hallmark in Oncovirus/Cytomegalovirus Infections and Cytomegalovirus' Resemblance to Oncoviruses.Cells · 2024Review
- Activation of the CCL22/CCR4 causing EMT process remodeling under EZH2-mediated epigenetic regulation in cervical carcinoma.Journal of Cancer · 2024Article
- Review
- The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics.Current issues in molecular biology · 2023Article
- Epigenetic effects of short-chain fatty acids from the large intestine on host cells.microLife · 2023Review
- Galectin-9 Expression is Correlated to Cervical Squamous Cell Carcinoma Progression and Overall Survival.OncoTargets and therapy · 2023Article
- Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation.Histology and histopathology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent infection with high‑risk human papillomavirus is known to cause cervical cancer. The binding of the costimulatory factors, Tim‑3 and galectin‑9, can cause immune tolerance and lead to immune escape during carcinogenesis. Epigenetic regulation is essential for Tim‑3/galectin‑9 expression, which affects the outcome of local cervical cancer infection. Hence, exploring the epigenetic regulatory mechanisms of costimulatory signaling by Tim‑3/galectin‑9 is of great interest for investigating the mechanisms through which these proteins are regulated in cervical cancer tumorigenesis. In this study, we report that E2F‑1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine‑5)‑methyltransferase 3A (DNMT3A). EZH2 and H3K27me3 directly interact with the DNMT3A promoter region to negatively regulate its expression in HeLa cells. Moreover, the downregulated DNMT3A and the decreased methylation levels in HAVCR2/LGALS9 promoter regions in HeLa cells promoted the expression of Tim‑3/galectin‑9. Furthermore, the high expression of Tim‑3/galectin‑9 was associated with HPV positivity among patients with cervical cancer. Moreover, HAVCR2/LGALS9 promoter regions were hypermethylated in normal cervical tissues, and this hypermethylated status inhibited gene expression. On the whole, these findings suggest that EZH2, H3K27me3 and DNMT3A mediate the epigenetic regulation of the negative stimulatory molecules, Tim‑3 and galectin‑9 in cervical cancer which is associated with HPV18 infection.
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