网络毒理学和门德尔随机化揭示了甲基甲酸诱导的甲状腺癌的病原性因素
Jiao Wang1,2,3, Dandan Chen1,2,3, Junping Zhang1,2,3
1Department of Endocrine and Metabolism, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University.
European thyroid journal
|January 7, 2026
概括
暴露于单乙酸盐可能会增加甲状腺癌的风险. 网络毒理学确定了10个基因,包括ESR1和SKP2,作为潜在的因果关系,揭示了癌症发展中的关键生物机制.
科学领域:
- 环境毒理学环境毒理学
- 分子瘤学分子瘤学
- 网络药理学网络药理学
背景情况:
- 单乙烯甲酸 (MEHP) 是一种常见的环境甲酸代谢物,与甲状腺癌风险增加有关.
- 了解将MEHP暴露与甲状腺癌相关的分子机制对于风险评估和预防至关重要.
研究的目的:
- 使用网络毒理学预测MEHP诱导的甲状腺癌的分子发起者.
- 探索与MEHP相关的甲状腺癌发生的因果关系和生物学途径.
主要方法:
- 综合多个数据库分析 (PubChem,CTD,STITCH,GeneCards,OMIM) 以确定候选基因.
- 孟德尔随机化 (MR) 分析使用IEU数据库和表达量化特征位点 (eQTLs) 作为工具变量 (IVs).
- 基因本体学 (GO) 和基因和基因组的京都百科全书 (KEGG) 丰富分析,蛋白质-蛋白质相互作用 (PPI) 网络构建和分子对接模拟.
主要成果:
- 确定了10个MEHP相关的基因,与甲状腺癌有潜在的因果关系.
- 丰富分析显示了参与细胞内受体信号传递,对雌醇的反应,核受体活性和癌症途径 (细胞循环,托代谢) 的参与.
- 一个PPI网络突出显示了5个核心基因 (ESR1,SKP2,CASP8,ARNT,CDKN1B) 作为关键介质,分子对接表明与MEHP的直接相互作用.
结论:
- 提出了10个基因作为MEHP诱导的甲状腺癌的潜在媒介.
- 突出了ESR1,SKP2,CASP8,ARNT和CDKN1B作为潜在推动甲状腺癌发病的核心因素.
- 提供了对环境暴露相关的甲状腺癌背后的分子机制的见解.
更多相关视频
16:02Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
3.2K
07:08Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
6.5K
相关概念视频
Types of Toxins
3.1K
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
3.1K
Mutagenicity 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
Toxic Reactions: Overview
1.8K
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
1.8K
Synthesis and Regulation of Thyroid Hormones
7.1K
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
7.1K
Cancer Prevention
7.6K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
7.6K
