Rad18在抑制致癌物和瘤基因驱动的突变发生的不同作用in vivo
Jay R Anand1, Bethany Wagner Brown1, Jitong Lou2
1Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
NAR cancer
|January 21, 2026
概括
通过促进精确的DNA损伤修复,DNA修复蛋白RAD18抑制了口腔癌的发展. 在这种情况下,RAD18缺乏会加速口腔瘤的形成,并增加特定突变,这表明瘤抑制作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- RAD18激活Y家族转化合成 (TLS) DNA聚合酶,这些聚合酶耐受DNA损伤,但可能容易发生错误.
- RAD18经常在癌细胞中过度表达和激活,但其在癌症基因组塑造和瘤发生中的作用尚未完全理解.
研究的目的:
- 研究RAD18状态对化学诱导和瘤基因驱动的瘤发生的影响.
- 确定RAD18是否影响口腔状细胞癌 (OSCC) 的发展和突变格局.
主要方法:
- 在具有不同Rad18基因状态 (Rad18-/-与Rad18+/+) 的小鼠中使用了4-尼托基诺林-1-氧化物 (4NQO) 化学致癌模型.
- 分析了Rad18和TLS聚合酶mRNA表达的口腔上皮细胞.
- 在诱导的OSCC上进行了外体序列测序,以确定突变配置文件.
- 研究了Rad18在KrasG12D诱导的肺癌发生模型中的作用.
主要成果:
- 与Rad18+/+小鼠相比,慢性4NQO治疗加速了Rad18-/-小鼠的口腔瘤发病.
- 与Rad18+/+小鼠相比,来自Rad18-/-小鼠的OSCC外体显示出G(C)>T(A) 转变的增加.
- 在KrasG12D诱导的肺癌模型中,Rad18缺乏没有影响瘤发生率或突变.
结论:
- RAD18促进了4NQO诱导的DNA病变的无错误绕道,抑制了4NQO诱导的口腔癌发生.
- RAD18表现出特定于环境的瘤抑制活性.
- RAD18可能塑造人类癌症基因组,并影响瘤发生,特别是在类似于4NQO的环境暴露的情况下.
更多相关视频
07:04Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli
Published on: February 5, 2019
20.6K
09:58Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
3.1K
相关概念视频
01:25Mutagenicity and Carcinogenicity
1.9K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.9K
01:16Repressed Memory
504
Repressed memories are a psychological phenomenon where memories of traumatic events are unconsciously blocked from a person's awareness. This process occurs as a defense mechanism, protecting the mind from the emotional impact of distressing or painful experiences. For example, a person who has experienced childhood trauma may grow up with no conscious recollection of the event. In such cases, the memories are thought to be buried deep within the subconscious, inaccessible to the conscious...
504
01:33Cancer-Critical Genes I: Proto-oncogenes
11.2K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.2K
01:21Repressible Operon: trp Operon
1.4K
The trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
1.4K
01:16In-vitro Mutagenesis
16.1K
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
16.1K
01:27ATP Driven Pumps I: An Overview
9.7K
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
9.7K