在癌症中通过其替代拼接变体DAPK1-215调节DAPK1表达
QingShui Wang1, ShuYun Weng2, WenTing Zhong3
1Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China. wangqingshui@fjnu.edu.cn.
Journal of translational medicine
|January 20, 2025
概括
一种新的拼接变体,DAPK1-215,在死亡相关蛋白激酶1 (DAPK1) 表达上起到分子制动作用,影响癌细胞迁移和入侵. DAPK1-215 作为肝癌的预后标志物.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 遗传学 遗传学 是一个
背景情况:
- 死亡相关蛋白激酶1 (DAPK1) 是一种涉及细胞死亡,发育和疾病的氨酸/氨酸激酶.
- 在癌症中DAPK1表达的调节还不清楚.
研究的目的:
- 研究DAPK1拼接变体DAPK1-215在各种癌症类型中的表达和功能作用.
- 阐明DAPK1-215影响DAPK1表达和癌细胞行为的机制.
- 评估DAPK1-215和DAPK1在肝癌中的预后意义.
主要方法:
- 在癌细胞系中使用qRT-PCR和西式涂抹量化DAPK1和DAPK1-215表达.
- 在斑马鱼模型中评估细胞迁移,入侵和细胞增殖在体外和转移潜力.
- 使用RNA拉下和CLIP-seq来识别RNA结合蛋白.
- 分析了临床肝癌样本的预后相关性.
主要成果:
- DAPK1-215通过降低肝脏,脏和胃癌细胞中的mRNA稳定性来降低DAPK1的表达.
- DAPK1-215在肝癌和癌中促进了迁移和入侵,但在胃癌细胞中抑制了这些.
- 死亡盒酶3X连接 (DDX3X) 稳定了DAPK1和DAPK1-215mRNA,这表明它们在结合方面存在竞争.
- 高的DAPK1-215水平与肝癌的预后不佳相关,而高的DAPK1预测了更好的结果.
结论:
- DAPK1-215作为DAPK1表达的分子制动作用,以情境依赖的方式影响癌细胞迁移和入侵.
- DAPK1-215是恶性进展的重要调节剂,也是肝癌潜在的预后标志物.
相关概念视频
Abnormal Proliferation
4.4K
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...
4.4K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
Interactions Between Signaling Pathways
6.2K
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...
6.2K
MAPK Signaling Cascades
5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K
RNA Splicing
56.0K
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...
56.0K
Alternative RNA Splicing
20.9K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
20.9K


