通过招募CtBP1来调节NF-κB通路,ZNF623有助于乳腺癌的进展
Zihan Zhang1, Peiyang Fang2, Jinging Zhu2
1Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China; Beijing Clinical Research Institute, Beijing, 100050, China.
Biochemical and biophysical research communications
|July 3, 2024
概括
乳腺癌中ZNF623基因升高,预测预后不佳,促进瘤生长和转移. 它通过与CtBP1.1相互作用抑制NF-κB抑制剂来起作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 乳腺癌是全球主要的恶性瘤.
- 染色体8q24的放大在乳腺癌中很常见.
- 位于8q24的ZNF623在乳腺癌中没有得到充分的研究.
研究的目的:
- 研究ZNF623的表达,它的预后价值,以及它在乳腺癌中的生物学作用.
- 阐明ZNF623在乳腺癌发生过程中的作用背后的分子机制.
主要方法:
- 对ZNF623 mRNA表达和生存数据的生物信息分析.
- 在ZNF623操纵后的体外功能测定 (细胞活力,迁移,增殖).
- 路西法雷斯记者测量转录活动.
- 同免疫沉和质谱测量以识别相互作用的蛋白质.
- 染色体免疫沉 (ChIP) 来识别ZNF623的基因.
- 流细胞计测试以评估信号通路的激活.
主要成果:
- 乳腺癌中ZNF623的表达显著上调,与患者生存率较差相关.
- 增加ZNF623促进乳腺癌细胞的增殖和迁移.
- ZNF623作为转录抑制剂,与CtBP1相互作用.
- ZNF623/CtBP1复合体抑制了参与NF-κB通路的基因,例如COMMD1,NFKBIL1,PYCARD和BRMS1.
- 击败ZNF623降低了p65酸化,表明NF-κB活动的调节.
结论:
- ZNF623是乳腺癌不良结果的预后标志物.
- 通过增强增殖和转移,ZNF623促进瘤的进展.
- ZNF623招募CtBP1以转录抑制NF-κB抑制剂,从而推动乳腺癌的发展.
相关概念视频
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
The Nucleolus
8.8K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.8K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K


