不稳定的3'UTR元素在耐药ERBB2+癌症模型中治疗性降解ERBB2mRNA
Chidiebere U Awah1,2, Yana Glemaud1, Fayola Levine1,2
1Department of Biological Sciences, Hunter College of The City University of New York, New York City, NY, United States.
Frontiers in genetics
|June 26, 2023
概括
研究人员开发了一种针对耐药癌症的ERBB2mRNA的新疗法. 这种方法降低了ERBB2转录,减少了致癌蛋白,并为难以治疗的ERBB2+癌症提供了一种新的治疗方式.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物技术是生物技术.
背景情况:
- 分子向疗法面临癌症耐药性的挑战,特别是在ERBB2+癌症中.
- ERBB2+癌症往往对现有的ERBB2向治疗具有抗性,导致临床结果不佳.
研究的目的:
- 研究3'未翻译区域 (3'UTR) 聚U序列在ERBB2 mRNA稳定中的作用.
- 开发一种新的治疗策略,通过降解ERBB2mRNA来克服ERBB2向治疗耐药性.
主要方法:
- 工程ERBB2 mRNA 3'UTR序列,以创建不稳定的形式.
- 利用这些工程序列来超越和降解内源ERBB2mRNA.
- 评估了这种方法在野生类型和耐药癌细胞中的疗效in vitro和in vivo.
主要成果:
- 工程序列成功降解了ERBB2的转录.
- 这种降解导致ERBB2蛋白在各种癌症细胞类型中的显著损失.
- 该方法在标准和耐药癌症模型中都表现出有效性.
结论:
- 准ERBB2 mRNA稳定性为ERBB2+癌症提供了一种新的治疗方式.
- 这一策略有效地降低了ERBB2蛋白水平,克服了对当前疗法的耐药性.
- 开发的技术提供了一种安全有效的方法来控制ERBB2mRNA和其他瘤信号.
相关概念视频
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
mRNA Stability and Gene Expression
5.7K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.7K
Destabilization of Microtubules
2.8K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.8K
Mitogens and the Cell Cycle
6.6K
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...
6.6K
Treatment Resistant Cancers
3.4K
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...
3.4K
Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K


