相关实验视频

Updated: Jun 23, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

TGF-β1通过m6A修改调节FOXA1转化效率,促进胆囊癌转移

Zhenheng Wu^1,2,3,4, Qiming Ke^1,2,3,4, Lei Jiang^1,2

¹Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.

Cell death & disease

|June 17, 2024

概括

转化生长因子β1 (TGF-β1) 通过降低FOXA1蛋白水平,促进胆囊癌 (GBC) 转移. 这通过N6-甲基氨酸 (m6A) 修改发生,这降低了FOXA1 mRNA翻译效率.

科学领域:

分子瘤学分子瘤学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
癌症转移癌症转移

背景情况:

转化生长因子β1 (TGF-β1) 在癌症转移中至关重要.
N6-甲基氨酸 (m6A) 是一个关键的mRNA修饰,但其在TGF-β1驱动的胆囊癌 (GBC) 转移中的作用尚不清楚.
在GBC中TGF-β1,m6A和mRNA翻译之间的相互作用需要进一步研究.

研究的目的:

阐明TGF-β1影响GBC转移的机制.
研究m⁶在调节TGF-β1信号传递下的FOXA1翻译效率中的修饰的作用.
探索向GBC中的TGF-β1 / FOXA1通路的治疗潜力.

主要方法:

在GBC中对FOXA1和TGF-β1表达的相关性分析.
在体外测试 (细胞迁移,上皮-介质细胞转换 - - EMT) 和体内转移模型.
多基因组造型,m⁶ARNA免疫沉降 (MeRIP),RNA免疫沉降 (RIP),双露西法酶记者测定和位点定向的突变发生.

主要成果:

过度表达FOXA1抑制了GBC细胞中的TGF-β1诱导的迁移和EMT.
TGF-β1通过促进其编码序列 (CDS) 中的m⁶A修改来抑制FOXA1mRNA翻译效率.
ALKBH5通过抑制FOXA1mRNA上的m6A修饰来抵消TGF-β1的作用,从而增加FOXA1蛋白表达.

结论:

TGF-β1通过通过m⁶A修改降低FOXA1翻译效率来促进GBC转移和EMT.
ALKBH5通过去甲基化FOXA1mRNA发挥保护作用,反对TGF-β1的抑制作用.
针对TGF-β1 / m6 / A / FOXA1轴为GBC转移提供了一个潜在的治疗策略.

更多相关视频

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

Analysis of Liver Microenvironment During Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish

Analysis of Liver Microenvironment During Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish

Published on: April 1, 2021

相关概念视频

TGF - β Signaling Pathway

TGF - β Signaling Pathway

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...