ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Polycomb repressor complex-2 is a novel target for mesothelioma therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis.Oncotarget · 2016Pooled it
- The Role of EZH2 ın Malıgnant Pleural Mesothelıoma and Beyond: Current Practıce and Future Perspectıves.Current oncology reports · 2026Review
- Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Methylation biomarkers can distinguish pleural mesothelioma from healthy pleura and other pleural pathologies.Molecular oncology · 2026Article
- Molecular Mechanisms of Tumor Progression and Novel Therapeutic and Diagnostic Strategies in Mesothelioma.International journal of molecular sciences · 2025Review
- Review
- Review
- EZH2: An Accomplice of Gastric Cancer.Cancers · 2023Review
- Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.Scientific reports · 2022Article
- Epigenetic modulation enhances immunotherapy for pancreatic ductal adenocarcinoma.Clinical & translational immunology · 2022Article
- DZNep promotes mouse bone defect healing via enhancing both osteogenesis and osteoclastogenesis.Stem cell research & therapy · 2021Article
- Novel and Promising Systemic Treatment Approaches in Mesothelioma.Current treatment options in oncology · 2021Review
- Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids.International journal of molecular sciences · 2021Article
- Identification of genes and pathways involved in malignant pleural mesothelioma using bioinformatics methods.BMC medical genomics · 2021Article
- BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors.Frontiers in oncology · 2021Article
- UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021Article
- Article
- Molecular characterization of diffuse malignant peritoneal mesothelioma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Application of immunohistochemistry in diagnosis and management of malignant mesothelioma.Translational lung cancer research · 2020Review
- Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
purposePolycomb group (PcG) proteins are critical epigenetic mediators of stem cell pluripotency, which have been implicated in the pathogenesis of human cancers. This study was undertaken to examine the frequency and clinical relevance of PcG protein expression in malignant pleural mesotheliomas (MPM). EXPERIMENTAL
designMicroarray, quantitative reverse transcriptase PCR (qRT-PCR), immunoblot, and immunohistochemistry techniques were used to examine PcG protein expression in cultured MPM, mesothelioma specimens, and normal mesothelial cells. Lentiviral short hairpin RNA techniques were used to inhibit EZH2 and EED expression in MPM cells. Proliferation, migration, clonogenicity, and tumorigenicity of MPM cells either exhibiting knockdown of EZH2 or EED, or exposed to 3-deazaneplanocin A (DZNep), and respective controls were assessed by cell count, scratch and soft agar assays, and murine xenograft experiments. Microarray and qRT-PCR techniques were used to examine gene expression profiles mediated by knockdown of EZH2 or EED, or DZNep.
resultsEZH2 and EED, which encode components of polycomb repressor complex-2 (PRC-2), were overexpressed in MPM lines relative to normal mesothelial cells. EZH2 was overexpressed in approximately 85% of MPMs compared with normal pleura, correlating with diminished patient survival. Overexpression of EZH2 coincided with decreased levels of miR-101 and miR-26a. Knockdown of EZH2 orEED, or DZNep treatment, decreased global H3K27Me3 levels, and significantly inhibited proliferation, migration, clonogenicity, and tumorigenicity of MPM cells. Common as well as differential gene expression profiles were observed following knockdown of PRC-2 members or DZNep treatment.
conclusionsPharmacologic inhibition of PRC-2 expression/activity is a novel strategy for mesothelioma therapy.
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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.