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NRF2/KEAP1 通路在胶质母细胞瘤中的作用:药理学意义。

The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications.

机构信息

Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

Med Oncol. 2022 May 15;39(5):91. doi: 10.1007/s12032-022-01693-0.

Abstract

Glioblastoma multiforme (GBM) grade IV glioma is the most frequent and deadly intracranial cancer. This tumor is determined by unrestrained progression, uncontroled angiogenesis, high infiltration and weak response to treatment, which is chiefly because of abnormal signaling pathways in the tumor. A member related to the Cap 'n' collar family of keypart-leucine zipper transcription agents-the transcription factor NF-E2-related factor 2 (Nrf2)-regulates adaptive protection answers by organized upregulation of many genes that produce the cytoprotective factors. In reply to cellular pressures types such as stresses, Nrf2 escapes Kelch-like ECH-related protein 1 (Keap1)-facilitated suppression, moves from the cytoplasm towards the nucleus and performs upregulation of gene expression of antioxidant responsive element (ARE). Nrf2 function is related tocontrolling many types of diseases in the human specially GBM tumor.Thus, we will review the epigeneticalregulatory actions on the Nrf2/Keap1 signaling pathway and potential therapeutic options in GBM by aiming the stimulation of Nrf2.

摘要

多形性胶质母细胞瘤(GBM)IV 级胶质瘤是最常见和最致命的颅内肿瘤。这种肿瘤的特征是不受控制的进展、不受控制的血管生成、高浸润和对治疗的反应较弱,这主要是由于肿瘤中异常的信号通路。Cap'n'collar 家族的关键亮氨酸拉链转录因子之一 - 转录因子 NF-E2 相关因子 2(Nrf2)- 通过组织上调产生细胞保护因子的许多基因来调节适应性保护反应。为了应对细胞压力类型,如应激,Nrf2 逃避 Kelch-like ECH-related protein 1(Keap1)介导的抑制,从细胞质转移到细胞核,并上调抗氧化反应元件(ARE)的基因表达。Nrf2 功能与控制人类特别是 GBM 肿瘤的许多类型的疾病有关。因此,我们将综述 Nrf2/Keap1 信号通路的表观遗传调控作用以及通过刺激 Nrf2 治疗 GBM 的潜在治疗选择。

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