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EZH2 as a new therapeutic target in brain tumors: Molecular landscape, therapeutic targeting and future prospects
Mahshid Deldar Abad Paskeh1, Atefeh Mehrabi1, Mohammad Hossein Gholami2
1Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Abstract:
Brain tumors are responsible for high mortality and morbidity worldwide. The brain tumor treatment depends on identification of molecular pathways involved in progression and malignancy. Enhancer of zeste homolog 2 (EZH2) has obtained much attention in recent years in field of cancer therapy due to its aberrant expression and capacity in modulating expression of genes by binding to their promoter and affecting methylation status. The present review focuses on EZH2 signaling in brain tumors including glioma, glioblastoma, astrocytoma, ependymomas, medulloblastoma and brain rhabdoid tumors. EZH2 signaling mainly participates in increasing proliferation and invasion of cancer cells. However, in medulloblastoma, EZH2 demonstrates tumor-suppressor activity. Furthermore, EZH2 can regulate response of brain tumors to chemotherapy and radiotherapy. Various molecular pathways can function as upstream mediators of EZH2 in brain tumors including lncRNAs and miRNAs. Owing to its enzymatic activity, EZH2 can bind to promoter of target genes to induce methylation and affects their expression. EZH2 can be considered as an independent prognostic factor in brain tumors that its upregulation provides undesirable prognosis. Both anti-tumor agents and gene therapies such as siRNA have been developed for targeting EZH2 in cancer therapy.
Insights
Enhancer of zeste homolog 2 (EZH2) plays a key role in brain tumor progression and malignancy. Targeting EZH2 shows promise for novel cancer therapies, though its function varies by tumor type.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Brain tumors cause significant global mortality and morbidity.
- Understanding molecular pathways is crucial for effective brain tumor treatment.
- Enhancer of zeste homolog 2 (EZH2) is implicated in cancer due to its gene regulatory functions.
Purpose of the Study:
- To review the role of EZH2 signaling in various brain tumors.
- To explore EZH2's impact on cancer cell proliferation, invasion, and treatment response.
- To discuss upstream regulators and therapeutic strategies targeting EZH2.
Main Methods:
- Literature review of studies on EZH2 in brain tumors.
- Analysis of EZH2's molecular mechanisms, including gene promoter binding and methylation.
- Investigation of EZH2's prognostic value and therapeutic targeting.
Main Results:
- EZH2 promotes proliferation and invasion in most brain tumors (glioma, glioblastoma, astrocytoma, ependymomas, brain rhabdoid tumors).
- EZH2 exhibits tumor-suppressor activity in medulloblastoma.
- EZH2 influences response to chemotherapy and radiotherapy and acts as an independent prognostic factor.
Conclusions:
- EZH2 signaling is a critical factor in brain tumor development and progression.
- EZH2's dual role (oncogenic/suppressor) necessitates context-specific therapeutic strategies.
- Targeting EZH2 with agents or gene therapy (siRNA) offers potential for novel brain tumor treatments.
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