由矩阵度诱导的NARF通过增强LEF1介导的转录促进肝细胞癌的进展
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Biochimica et biophysica acta. Molecular cell research
|February 8, 2026
概括
核前胺A识别因子 (NARF) 是一种新型基因,在肝癌中由矩阵刚性驱动. 通过激活Wnt信号,NARF促进肝细胞癌 (HCC) 的生长和转移.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 肝纤维化和肝硬化形成了一个硬的细胞外基质 (ECM) 利基,与肝细胞癌 (HCC) 的发展有关.
- 对于ECM刚性驱动HCC进展的确切机制尚未完全理解.
研究的目的:
- 鉴定HCC中由矩阵刚度调节的新型基因.
- 阐明核前胺A识别因子 (NARF) 在HCC进展和转移中的作用.
主要方法:
- 确定了NARF作为一个由YAP调节的矩阵刚度响应基因.
- 评估了HCC组织中的NARF表达,并将其与患者的结果相关联.
- 研究了NARF在HCC细胞增殖,迁移,入侵和EMT中的功能作用,在体外和体内.
- 利用RNA测序来识别与NARF相关的信号通路.
- 进行了涉及EP300,H3K27乙化和LEF1.1的机械学研究.
主要成果:
- 在HCC组织中,NARF表达被上调,并与预后不佳有关.
- NARF的降解抑制了HCC细胞的增殖,迁移,入侵和EMT,并减少了体内转移.
- 过度表达NARF增强了这些致癌过程.
- 通过招募EP300来增强LEF1依赖转录,NARF积极调节Wnt信号.
- LEF1是NARF致癌活性的一个关键下游效应因子.
结论:
- 在HCC中,NARF是一种通过YAP转录调节的性反应基因.
- 通过YAP介导的LEF1和Wnt信号的激活,NARF促进了HCC的生长和转移.
- NARF代表了一个潜在的预后生物标志物和HCC的治疗目标.
相关概念视频
Transcription Factors
82.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.8K
Master Transcription Regulators
7.8K
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...
7.8K
The Eukaryotic Promoter Region
18.9K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.9K
Transcription
157.1K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
157.1K
Eukaryotic Transcription Activators
12.9K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.9K
Transcription Attenuation in Prokaryotes
18.5K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.5K


