向AHR通过ELAVL1-DCK通路增加胰腺癌细胞对吉姆西塔的敏感性
Darius Stukas1, Aldona Jasukaitiene1, Arenida Bartkeviciene1
1Surgical Gastroenterology Laboratory, Institute for Digestive Research, Lithuanian University of Health Sciences, Eiveniu 4, 50103 Kaunas, Lithuania.
International journal of molecular sciences
|September 9, 2023
概括
在胰腺癌中,氨酸碳化合物受体 (AHR) 和ELAVL1蛋白相互作用影响化学抵抗. 抑制 AHR 通过 ELAVL1-DCK 途径增强了对 gemcitabine 的敏感性,从而提供了新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 在胰腺管腺癌 (PDAC) 中,基碳化合物受体 (AHR) 被上调.
- AHR阻碍了人类抗原R (ELAVL1) 的核至细胞质穿,影响了向mRNA的稳定性和蛋白质表达,包括gemcitabine诱导的mRNA.
- 较高的AHR导致ELAVL1核封存,导致PDAC中的化学抵抗.
研究的目的:
- 为了研究AHR和ELAVL1在PDAC病变发生过程中的相互作用.
- 阐明AHR和ELAVL1在PDAC细胞增殖,迁移和化学抵抗中的作用.
- 探索 AHR 和 ELAVL1 相互作用背后的分子机制及其对宝石素敏感性的影响.
主要方法:
- 使用siRNA转染,对AHR和ELAVL1进行基因沉默.
- 定量实时聚合酶连锁反应 (qRT-PCR) 和西部污染 (WB) 用于RNA和蛋白质分析.
- 免疫沉 (IP) 试验用于检查ELAVL1蛋白与AHR mRNA之间的直接结合.
- 细胞活力,克隆原性和迁移测试以评估功能影响.
主要成果:
- AHR和ELAVL1表现出相互调节,并影响PDAC细胞的增殖,迁移和化学抵抗.
- 沉默ELAVL1破坏了目标mRNA的稳定,降低了细胞保护蛋白的表达.
- 通过AHR-ELAVL1-deoxycytidine kinase (DCK) 途径,AHR静音降低了细胞迁移和增殖,同时提高了通过AHR-ELAVL1-deoxycytidine kinase (DCK) 途径的凝素敏感性.
结论:
- 在PDAC中,AHR和ELAVL1的相互作用形成了一个负反循环.
- 抑制AHR的表达增加了PDAC细胞对gemcitabine的敏感性.
- ELAVL1-DCK通路对于在AHR抑制时调解凝胺敏感性至关重要.
更多相关视频
相关概念视频
02:57Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K
02:50Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
02:56Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
02:38Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K