EZHIP

更新于：2025-05-07

基本信息

别名

CATACOMB、CXorf67、EZH inhibitory protein

+ [1]

简介

Inhibits PRC2/EED-EZH1 and PRC2/EED-EZH2 complex function by inhibiting EZH1/EZH2 methyltransferase activity, thereby causing down-regulation of histone H3 trimethylation on 'Lys-27' (H3K27me3) (PubMed:29909548, PubMed:30923826, PubMed:31086175, PubMed:31451685). Probably inhibits methyltransferase activity by limiting the stimulatory effect of cofactors such as AEBP2 and JARID2 (PubMed:30923826). Inhibits H3K27me3 deposition during spermatogenesis and oogenesis (By similarity).

关联

100 项与 EZHIP 相关的临床结果

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100 项与 EZHIP 相关的转化医学

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0 项与 EZHIP 相关的专利（医药）

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项与 EZHIP 相关的文献（医药）

2025-04-01·Current Opinion in Pharmacology

Oncohistone-sculpted epigenetic mechanisms in pediatric brain cancer

Review

作者: Somyajit, Kumar ; Pandey, Deo Prakash

Chromatin dynamics, involving reversible changes in chromatin structure, shape key cellular processes and genomic integrity during development and proliferation, with disruptions leading to cancer. Histones, core components of chromatin and substrates for chromatin-modifying enzymes, play crucial roles in oncogenesis when misregulated or mutated. This is particularly pronounced in pediatric hind brain cancers, some of which are driven primarily by the oncohistone H3K27M and the recently identified oncohistone-mimic protein CXorf67/EZHIP. Notably, H3K27M and EZHIP-driven cancers exhibit low mutation burdens, highlighting the enigmatic role of non-mutational epigenetic reprogramming in oncogenesis beyond traditional paradigms of oncogene activation and tumor suppressor loss. Here, we review the impact of H3K27M and EZHIP-driven cancer mechanisms on chromatin and transcriptional dysregulation leading to aberrant cell fate determination, and their potential influence beyond gene activity, affecting broader cellular pathways. Illuminating these mechanisms is crucial for advancing treatment options for pediatric brain cancers, where therapeutic regimens are poorly defined.

2025-04-01·Virchows Archiv

H3 K27M mutation in rosette-forming glioneuronal tumors: a potential diagnostic pitfall

Article

作者: Broggi, Giuseppe ; Feletti, Alberto ; Masotto, Barbara ; Giovannoni, Isabella ; Rossi, Sabrina ; Marastoni, Elena ; Ammendola, Serena ; Barresi, Valeria

AbstractAccording to the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS), diffuse midline glioma H3 K27-altered is a grade 4 infiltrative glioma that arises from midline anatomical structures and is characterized by the loss of H3 K27me3 and co-occurring H3 K27M mutation or EZHIP overexpression. However, the H3 K27M mutation has also been observed in circumscribed gliomas and glioneuronal tumors arising in midline anatomical structures, which may result in diagnostic pitfalls.Rosette-forming glioneuronal tumor (RGNT) is a CNS WHO grade 1 neoplasm that histologically features neurocytic and glial components and originates in midline anatomical structures.This study aimed to assess whether RGNTs, similar to other midline tumors, may exhibit immunohistochemical loss of H3 K27me3 and harbor the H3 K27M mutation.All seven analyzed RGNTs displayed immunohistochemical loss of H3 K27me3 in all tumor cells or H3 K27me3 mosaic immunostaining. In one case, H3 K27me3 loss was associated with the H3 K27M mutation, whereas the other six cases did not exhibit any H3 mutations or EZHIP overexpression. During a follow-up period of 23 months, the H3 K27M-mutant case remained unchanged in size despite partial resection, indicating that the H3 mutation may not confer higher biological aggressiveness to RGNT.The immunohistochemical loss of H3 K27me3 co-occurring with the H3 K27M mutation may result in the potential misdiagnosis of RGNT, especially in cases of small biopsy specimens consisting of only the glial component.

2025-03-01·Journal of Neuro-Oncology

Prognostic value of immunohistochemical staining for H3K27me3 and EZH2 in astrocytoma, IDH-mutant

Article

作者: Amatya, Vishwa Jeet ; Takeshima, Yukio ; Khairunnisa, Novita Ikbar ; Horie, Nobutaka ; Onishi, Shumpei ; Go, Yukari ; Ozono, Iori ; Taguchi, Akira ; Yamasaki, Fumiyuki ; Yonezawa, Ushio

AbstractBackgroundH3 histone 27 lysine (H3K27) trimethylation (H3K27me3), which is catalyzed by enhancer of zeste homolog 2 (EZH2), regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a diagnostic marker for diffuse midline glioma and as a surrogate marker to distinguish posterior fossa ependymoma A and B. However, the clinical significance of the EZH2–H3K27me3 axis in astrocytoma, IDH-mutant has not been reported, prompting this investigation.MethodsThirty-three patients with astrocytoma, IDH-mutant treated at our institute were included in this study. Immunohistochemistry (IHC) targeting H3K27me3, H3K27M, EZH2, EZH inhibitory protein, IDH1-R132H, p53, ATRX, Ki-67, and MTAP was performed. Kaplan–Meier analysis and Cox regression analysis were performed to analyze the correlations of overall survival (OS) and progression-free survival (PFS) with various factors, including age, World Health Organization (WHO) grade, the extent of resection, and immunohistochemical results.ResultsThe mean patient age was 40.6 ± 11.0 years. IHC for H3K27me3 was positive in 19 patients and negative in 14 patients. The WHO grade and Ki-67 index were significantly higher in the H3K27me3-positive group (p = 0.004 and p = 0.024, respectively). OS and PFS were significantly shorter in the H3K27me3-positive group (p = 0.002 and p = 0.026, respectively). Furthermore, the H3K27me3 and EZH2 double-positive group was associated with a higher WHO grade and higher Ki-67 index (p = 0.001 and p = 0.024, respectively). In the analysis of patients with WHO grade 2/3, double positivity for H3K27me3 and EZH2 was linked to significantly shorter OS and PFS (p = 0.0053 and p = 0.0048, respectively).ConclusionPositivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.

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