DDX3X突变和爱斯坦-巴尔病毒合作诱导R循环依赖性瘤发生
Hua-Man Cai1, Yu-Ran Qiu1, Yun Tan1
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell reports
|September 6, 2025
概括
通过启用爱斯坦-巴尔病毒 (EBV) 溶解基因BNLF2b,RNA螺旋酶DDX3X的突变会损害先天免疫力并促进癌症. 这导致R循环积累和基因组不稳定, 提供新的治疗点.
科学领域:
- 癌症学
- 病毒学
- 分子生物学
背景情况:
- 在炎症酶激活和抗病毒反应中涉及RNA螺旋酶DDX3X.
- 在淋巴细胞癌中观察到分散的DDX3X突变.
- 爱斯坦-巴尔病毒 (EBV) 在瘤发生过程中起作用.
研究的目的:
- 在淋巴癌中描述DDX3X突变的常见特征.
- 阐明DDX3X突变在EBV驱动的瘤发生中的作用.
- 研究DDX3X突变与EBV之间的功能相互作用.
主要方法:
- 用分子动力学模拟和结晶来研究DDX3X突变.
- 使用了有条件的诺金转基因小鼠 (Ddx3x^449_450ET>DP).
- 研究了埃托波西德对DDX3X突变瘤的影响.
主要成果:
- DDX3X突变会损害STING/IRF-7/IFN-α/β介导的天生的免疫力.
- 突变导致EBV光基因BNLF2b的过度表达和R循环形成的增加.
- 在小鼠中,BNLF2b的表达会诱导R循环的积累,基因组的不稳定性,以及异常的免疫细胞增殖,从而促进恶性瘤.
- 在DDX3X突变型BNLF2b阳性瘤中,乙氧治疗会引发合成致死性.
结论:
- DDX3X突变与EBV相互作用,驱动R循环依赖的瘤发生.
- 这些发现揭示了EBV的致病机制,并建议R循环向治疗.
- 这项研究提供了涉及RNA螺旋酶变化的疾病的见解.
相关概念视频
Rous Sarcoma Virus (RSV) and Cancer
5.4K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
5.4K
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Mechanisms of Retrovirus-induced Cancers
5.2K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.2K
Non-LTR Retrotransposons
11.8K
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...
11.8K


