The CNC-family transcription factor NRF3: A crucial therapeutic target for cancer treatment

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Liangwen Yan , Xinyan Li , Jiayi Xu , Shenkang Tang , Gang Wang , Mengjiao Shi , Pengfei Liu
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引用次数: 0

Abstract

The CNC-bZIP family member NRF3 (NFE2L3) has received limited attention since its discovery. However, recent research has gradually revealed its biological functions, such as involvement in the regulation of cell differentiation, lipid metabolism, and malignant cell proliferation. Under physiological conditions, NRF3 is anchored to the endoplasmic reticulum within the cytoplasm and is biologically inactive. Upon cellular exposure to microenvironmental stresses such as oxidative stress, NRF3 translocates to the nucleus, binds to DNA, and acts as a transcription factor by inducing or repressing the expression of various genes. In terms of tumor regulation, NRF3 exhibits a dual role. It can function as a tumor suppressor to prevent the malignant progression of tumor tissues, protecting the organism from harm. Conversely, current research indicates that NRF3 plays a tumor-promoting role in most tumor tissues. NRF3 enhances the proliferation, migration and invasion of tumor cells by regulating cell cycle-related proteins and enhancing proteasome assembly to degrade tumor suppressors. Studies correlating NRF3 expression with clinical tumor features have found that elevated NRF3 expression is often associated with poor prognoses in various cancers, with patients exhibiting higher NRF3 expression typically having lower survival rates. Several studies suggest that NRF3 could serve as a clinical diagnostic and prognostic marker for tumors. Finally, from the clinical perspective, exploring the feasibility of inhibiting NRF3 activity in tumor treatment provides new insights for the development of NRF3-targeted oncological therapies.

Abstract Image

CNC-bZIP家族成员NRF3(NFE2L3)自发现以来受到的关注有限。然而,近年来的研究逐渐揭示了它的生物学功能,如参与细胞分化、脂质代谢和恶性细胞增殖的调控。在生理条件下,NRF3 固定在细胞质内的内质网中,没有生物活性。当细胞受到氧化应激等微环境压力时,NRF3 会转位到细胞核,与 DNA 结合,并作为转录因子诱导或抑制各种基因的表达。在肿瘤调控方面,NRF3 具有双重作用。它可以作为肿瘤抑制因子,阻止肿瘤组织的恶性发展,保护机体免受伤害。相反,目前的研究表明,NRF3 在大多数肿瘤组织中发挥着促瘤作用。NRF3 通过调节细胞周期相关蛋白和增强蛋白酶体组装以降解肿瘤抑制因子,从而增强肿瘤细胞的增殖、迁移和侵袭。将 NRF3 表达与临床肿瘤特征相关联的研究发现,NRF3 表达升高往往与各种癌症的不良预后有关,NRF3 表达较高的患者通常生存率较低。一些研究表明,NRF3 可作为肿瘤的临床诊断和预后标志物。最后,从临床角度来看,探索在肿瘤治疗中抑制 NRF3 活性的可行性为开发 NRF3 靶向肿瘤疗法提供了新的思路。
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来源期刊
CiteScore
12.30
自引率
0.00%
发文量
218
审稿时长
32 days
期刊介绍: BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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