Kaur Parminder, Verma Shiv, Kushwaha Prem Prakash, Gupta Sanjay
Department of Urology, Case Western Reserve University, Cleveland, OH, 44016, USA; The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, 44016, USA.
Department of Urology, Case Western Reserve University, Cleveland, OH, 44016, USA; The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, 44016, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH, 44016, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, 44016, USA; Department of Nutrition, Case Western Reserve University, Cleveland, OH, 44016, USA; Division of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA.
Cancer Lett. 2023 Apr 28;560:216143. doi: 10.1016/j.canlet.2023.216143. Epub 2023 Mar 22.
Epigenetic modifications regulate critical biological processes that play a pivotal role in the pathogenesis of cancer. Enhancer of Zeste Homolog 2 (EZH2), a subunit of the Polycomb-Repressive Complex 2, catalyzes trimethylation of histone H3 on Lys 27 (H3K27) involved in gene silencing. EZH2 is amplified in human cancers and has roles in regulating several cellular processes, including survival, proliferation, invasion, and self-renewal. Though EZH2 is responsible for gene silencing through its canonical role, it also regulates the transcription of several genes promoting carcinogenesis via its non-canonical role. Constitutive activation of Nuclear Factor-kappaB (NF-κB) plays a crucial role in the development and progression of human malignancies. NF-κB is essential for regulating innate and adaptive immune responses and is one of the most important molecules that increases survival during carcinogenesis. Given the evidence that increased survival and proliferation are essential for tumor development and their association with epigenetic modifications, it seems plausible that EZH2 and NF-κB crosstalk may promote cancer progression. In this review, we expand on how EZH2 and NF-κB regulate cellular responses during cancer and their crosstalk of the canonical and non-canonical roles in a context-dependent manner.
表观遗传修饰调控着关键的生物学过程，这些过程在癌症发病机制中起着关键作用。Zeste同源物2增强子（EZH2）是多梳抑制复合物2的一个亚基，催化参与基因沉默的组蛋白H3赖氨酸27（H3K27）的三甲基化。EZH2在人类癌症中发生扩增，并在调节多个细胞过程中发挥作用，包括存活、增殖、侵袭和自我更新。尽管EZH2通过其经典作用负责基因沉默，但它也通过其非经典作用调节多个促进癌变的基因的转录。核因子-κB（NF-κB）的组成性激活在人类恶性肿瘤的发生和发展中起关键作用。NF-κB对调节先天性和适应性免疫反应至关重要，并且是在癌变过程中增加存活率的最重要分子之一。鉴于增加存活和增殖对肿瘤发展至关重要以及它们与表观遗传修饰的关联，EZH2和NF-κB之间的相互作用可能促进癌症进展似乎是合理的。在这篇综述中，我们详细阐述了EZH2和NF-κB在癌症期间如何调节细胞反应以及它们在依赖于背景的方式下经典和非经典作用的相互作用。
