失去ATRX可以通过染色体重塑抑制肉瘤细胞中I型干扰素的反应
Xinrui Wang1, Zige Jin1, Shanshan Tang1
1Department of Cell Biology, School of Life Sciences, Anhui Medical University Hefei 230032, Anhui, China.
American journal of cancer research
|September 11, 2023
概括
在肉瘤细胞中ATRX的丧失通过改变染色质来抑制干扰素-β (IFN-β) 反应. 在肉瘤患者中,ATRX突变与更差的预后和受损的IFN信号相关.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 瘤是一种常见于儿童和青少年的侵袭性介质细胞癌.
- 导致肉瘤进展的遗传变化需要进一步阐明.
- 了解这些机制对于改善治疗结果至关重要.
研究的目的:
- 研究ATRX (SWI/SNFDNA重塑家族成员) 在肉瘤进展中的作用.
- 为了确定ATRX功能丧失如何影响肉瘤细胞中干扰素反应.
- 探索ATRX突变在肉瘤预后中的临床相关性.
主要方法:
- 使用多种I:C刺激来模拟干扰素反应.
- 使用CRISPR/Cas9和siRNA用于ATRX耗尽.
- 进行RNA-sequencing (RNA-seq) 和ATAC-sequencing (ATAC-seq) 来分析基因表达和染色体可访问性.
主要成果:
- 在肉瘤细胞中,ATRX功能丧失显著抑制了IFNB1和其他细胞因子的表达.
- 在特定的肉瘤类型中,ATRX突变与更糟糕的预后和减少IFN-α/β反应有关.
- ATRX 枯竭改变了全球基因表达模式和染色质可访问性,表明它在转录调节中的作用.
结论:
- ATRX在调节肉瘤细胞中的I型干扰素信号传递方面发挥着关键作用.
- 失去ATRX功能会通过阻断IFN信号来损害抗瘤免疫反应.
- 准ATRX或相关途径可能为肉瘤治疗提供新的治疗策略.
相关概念视频
Loss of Tumor Suppressor Gene Functions
4.9K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
T Cell Types and Functions
1.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.1K
Experimental RNAi
6.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
Inheritance of Chromatin Structures
6.3K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.3K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
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


