ArticleEpigenetics2012
Heterogeneous epigenetic regulation of TIMP3 in prostate cancer.
Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review.International journal of molecular sciences · 2021Pooled it
- TMT-based proteomic profiling of serum reveals the impact of developmental stage and generation in beef cattle.Frontiers in veterinary science · 2026Article
- Epigenetic regulation of TIMP-3 expression in human macrophages via physiological and pharmacological modification of histone3 lysine27 (H3K27).Molecular biology reports · 2025Article
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Epigenetic Therapies in Melanoma-Targeting DNA Methylation and Histone Modification.Biomedicines · 2025Review
- The role of aberrant DNA methylation in cancer initiation and clinical impacts.Therapeutic advances in medical oncology · 2024Article
- Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer.International journal of environmental research and public health · 2022Article
- Epigenetic mechanisms underlying prostate cancer radioresistance.Clinical epigenetics · 2021Review
- MAb NJ001 inhibits lung adenocarcinoma invasiveness by directly regulating TIMP-3 promoter activity via FOXP1 binding sites.Thoracic cancer · 2020Article
- Review
- Further understanding of epigenetic dysfunction of the retinal pigment epithelium in AMD.Expert review of ophthalmology · 2020Article
- A Strong Decrease inFrontiers in oncology · 2019Article
- TIMP-3 as a therapeutic target for cancer.Therapeutic advances in medical oncology · 2019Review
- TIMP3 expression associates with prognosis in colorectal cancer and its novel arylsulfonamide inducer, MPT0B390, inhibits tumor growth, metastasis and angiogenesis.Theranostics · 2019Article
- Distinct prostate cancer-related mRNA cargo in extracellular vesicle subsets from prostate cell lines.BMC cancer · 2017Article
- Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers.BMC cancer · 2016Article
- The Clinical Utility of TIMP3 Expression in ACTH-Secreting Pituitary Tumor.Journal of molecular neuroscience : MN · 2016Article
- Article
- A novel action mechanism for MPT0G013, a derivative of arylsulfonamide, inhibits tumor angiogenesis through up-regulation of TIMP3 expression.Oncotarget · 2014Article
- Tumor necrosis factor-α and apoptosis induction in melanoma cells through histone modification by 3-deazaneplanocin A.The Journal of investigative dermatology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitor of metalloproteinase-3 (TIMP3) is a tumor suppressor gene frequently downregulated in prostate cancer. The mechanisms involved in TIMP3 transcriptional repression are not fully understood, but evidence suggests that promoter hypermethylation may not be the predominant epigenetic alteration in prostate cancer. To clarify this issue, we examined the contribution of both CpG site promoter methylation and histone modifications on TIMP3 downregulation. Using publicly available data sets, we confirmed that TIMP3 mRNA expression is decreased in prostate tumors relative to normal glands. Immunohistochemical analysis also showed decreased TIMP3 levels in high-grade primary tumors, but promoter hypermethylation was only detected in 6 of 28 (21%) high-grade specimens. Similarly, in prostate cancer cells, TIMP3 hypermethylation was only observed in DU145 cells. Treatment of DU145 cells with 5-aza-2'-deoxycytidine (5-Aza-CdR) restored TIMP3 expression, and this was significantly amplified by co-treating the cells with the HDAC inhibitor trichostatin A (TSA). Alternatively, in cells that did not exhibit aberrant TIMP3 methylation (LNCaP and PC3), TIMP3 expression could be upregulated by the combination of histone methylation inhibitor 3-Deazaneplanocin A (DZNep) and TSA. This reversal of transcriptional repression was associated with decreased H3K27me3 and increased H3K9ac histone marks at the TIMP3 promoter, as demonstrated by chromatin immunoprecipitation. Collectively, these results indicate that histone modifications can contribute to TIMP3 repression in the absence of promoter hypermethylation, and suggest that the combination of histone modifying agents could restore TIMP3 expression in prostate tumors harboring aberrant histone modifications at the TIMP3 promoter.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.