ArticleScientific reports2017
EZH2-mediated epigenetic silencing of TIMP2 promotes ovarian cancer migration and invasion.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- Epigenetic alterations in cancer metastasis: molecular mechanisms and implications for precision oncology.Frontiers in oncology · 2026Review
- Combined Assessment of EZH2 and EGFR as Potential Diagnostic Biomarkers for Epithelial Ovarian Tumors: Bioinformatics Analysis and Clinical Validation.International journal of women's health · 2026Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis.Experimental hematology · 2025Review
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway.iScience · 2025Article
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- Morphological Changes Induced by TKS4 Deficiency Can Be Reversed by EZH2 Inhibition in Colorectal Carcinoma Cells.Biomolecules · 2024Article
- Pharmacological inhibition of EZH2 using a covalent inhibitor suppresses human ovarian cancer cell migration and invasion.Molecular and cellular biochemistry · 2024Article
- The Ovary-Brain Connection.Cells · 2024Article
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- Review
- PRC2 loss drives MPNST metastasis and matrix remodeling.JCI insight · 2022Article
- Epigenetic modification regulates tumor progression and metastasis through EMT (Review).International journal of oncology · 2022Review
- Menin Enhances Androgen Receptor-Independent Proliferation and Migration of Prostate Cancer Cells.Molecules and cells · 2022Article
- Sevoflurane Offers Neuroprotection in a Cerebral Ischemia/Reperfusion Injury Rat Model Through the E2F1/EZH2/TIMP2 Regulatory Axis.Molecular neurobiology · 2022Article
- MiR-106b-5p Promotes Malignant Behaviors of Cervical Squamous Cell Carcinoma Cells by Targeting TIMP2.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Pulmonary medicine · 2022Review
- circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis.Open medicine (Warsaw, Poland) · 2022Article
- Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2). EZH2 overexpression inhibited TIMP2 expression and promoted proteolytic activities of matrix metalloproteinases 2 and 9 and vice versa. EZH2 promoted ovarian cancer invasion and migration, which could be largely reversed by TIMP2 down-regulation in vitro and in vivo. Both H3K27me3 inhibition and demethylation could reduce methylation of the TIMP2 promoter and finally reactivate TIMP2 transcription. The presence of EZH2 and H3K27me3 at the TIMP2 promoter was confirmed by chromatin immunoprecipitation. H3K27me3 and DNA methyltransferases at the promoter were significantly increased by EZH2 overexpression. These results suggest that EZH2 inhibits TIMP2 expression via H3K27me3 and DNA methylation, which relieve the repression of MMP and facilitate ovarian cancer invasion and migration.
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