拼接因子FUS通过对MDM2进行上调来促进PIT1血统PitNET的进展
Xu Wang1,2,3, Jiang Li1,2, Chenggang Jiang1,2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Theranostics
|January 9, 2026
概括
拼接因子FUS通过调节MDM2拼接来促进垂体瘤的生长. 用反感性寡核酸向这个过程会阻止瘤的进展,为PIT1系垂体神经内分泌瘤提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 剪接因子在mRNA处理中至关重要,并且与瘤进展有关.
- 异常拼接因子表达与垂体神经内分泌瘤 (PitNET) 侵入性相关.
- 这项研究研究了PIT1血统PitNET进展中的拼接因素.
研究的目的:
- 探索拼接因子在PIT1系 PitNET进展中的作用.
- 评估针对性拼接作为PitNET的治疗策略.
- 阐明FUS在PitNET开发中的功能.
主要方法:
- 在40个临床PitNET样本上进行基因表达分析.
- 转录组和RNA免疫沉降测序 (RIP-seq) 用于研究FUS介导的拼接.
- 迷你基因测定,Annexin V/PI和JC-1染色以验证拼接和亡.
主要成果:
- 在PIT1系PitNET中FUS表达升高与更高的增殖和较低的亡相关.
- 在FUS中,Knockdown诱导了前子跳转,并激活了p53通路.
- FUS通过外因子3的包含促进MDM2的全长转录,抑制p53.
结论:
- 在PitNET进展中,FUS是关键的拼接因素.
- 针对FUS介导的MDM2拼接可以恢复p53水平,并阻碍PitNET的生长.
- 这为PIT1血统PitNETs提出了一个新的治疗策略.
相关概念视频
Abnormal Proliferation
5.1K
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...
5.1K
Restarting Stalled Replication Forks
6.3K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.3K
The Spindle Assembly Checkpoint
3.7K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.7K
Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
RNA Splicing
60.3K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.3K
Separation of Sister Chromatids
4.3K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.3K


