Department 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.
Faculty of Veterinary Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran.
Biomed Pharmacother. 2022 Feb;146:112532. doi: 10.1016/j.biopha.2021.112532. Epub 2021 Dec 11.
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.
脑肿瘤是全球高死亡率和高发病率的主要原因。脑肿瘤的治疗取决于鉴定涉及进展和恶性的分子途径。由于其异常表达及其通过与启动子结合并影响甲基化状态来调节基因表达的能力，增强子的锌指蛋白 2（EZH2）在癌症治疗领域近年来受到了广泛关注。本文重点介绍了 EZH2 在脑肿瘤中的信号通路，包括神经胶质瘤、胶质母细胞瘤、星形细胞瘤、室管膜瘤、髓母细胞瘤和脑横纹肌样瘤。EZH2 信号通路主要参与了癌细胞的增殖和侵袭的增加。然而，在髓母细胞瘤中，EZH2 表现出肿瘤抑制活性。此外，EZH2 可以调节脑肿瘤对化疗和放疗的反应。在脑肿瘤中，多种分子通路可以作为 EZH2 的上游调节剂，包括长链非编码 RNA 和 microRNA。由于其酶活性，EZH2 可以与靶基因的启动子结合，诱导甲基化并影响其表达。EZH2 可以被认为是脑肿瘤的一个独立预后因素，其上调提供了不良的预后。已经开发了针对 EZH2 的抗肿瘤药物和基因治疗，如 siRNA，用于癌症治疗。
