多层次功能基因组学揭示了基于患者的3'未翻译区域突变的分子和细胞瘤性
Samantha L Schuster1, Sonali Arora2, Cynthia L Wladyka2
1Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Cell reports
|July 29, 2023
概括
基因3'未翻译区域 (3' UTR) 的体质突变可以驱动癌症. 这项研究发现,前列腺瘤中的这些突变显著影响基因表达和患者的结果,揭示了新的治疗点.
科学领域:
- 遗传学 遗传学 是一个
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 在3'未翻译区域 (3'UTR) 的体质突变是癌症基因失调的一个研究不足的机制.
- 这些3' UTR突变对mRNA稳定性和翻译的功能影响在很大程度上是未知的.
研究的目的:
- 为了研究3' UTR体质突变在晚期前列腺癌中的重要性.
- 识别功能性3' UTR变异并了解它们在瘤发生和患者预后中的作用.
主要方法:
- 在185个晚期前列腺瘤中识别和分析3' UTR体质变异.
- 开发和应用报告测试来测量突变对mRNA翻译和稳定性的影响.
- CRISPR-Cas9基因编辑用于验证特定变异的功能影响.
主要成果:
- 在3' UTR中发现了14497个单核酸突变,富含致癌途径和调控元素.
- 确定了数百种影响mRNA稳定性和翻译的功能变异.
- 证明特定的3' UTR突变增强细胞抗压能力,与患者预后不佳相关.
结论:
- 3' UTR体质突变在前列腺癌的进展中起着重要作用.
- 这些突变影响mRNA调节和细胞功能,提供潜在的治疗点.
- 这项研究扩大了对癌症发展中的调节区域的理解.
相关概念视频
Cancer-Critical Genes I: Proto-oncogenes
9.0K
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...
9.0K
Translation
15.0K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
15.0K
Mutagenicity and Carcinogenicity
1.3K
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...
1.3K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.5K
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...
7.5K
Non-LTR Retrotransposons
11.6K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.6K
Cancers Originate from Somatic Mutations in a Single Cell
12.0K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.0K


