表观遗传共同调节剂HCF-1通过O-GlcNAcylation依赖的途径促进肺癌
Priyanka P Srivastava1, Abhilash Dasari2, Saran Kumar1
1Kusuma School of Biological Sciences (KSBS), Indian Institute of Technology Delhi (IITD), Hauz Khas, New Delhi, India.
Molecular therapy. Oncology
|September 29, 2025
概括
宿主细胞因子-1 (HCF-1) 和与O相关的N-乙糖胺 (O-GlcNAc) 糖化在肺癌中受到上调. 它们的抑制减少了癌细胞的增殖,这表明它们是肺癌干预的关键目标.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 全球肺癌发病率正在上升,需要对其分子机制进行研究.
- 宿主细胞因子-1 (HCF-1) 是一种表观遗传调节剂,其通过O-链接的N-乙糖胺 (O-GlcNAc) 转移酶 (OGT) 的糖化与癌症有关.
- 在肺癌组织中观察到较高的O-GlcNAc和OGT水平.
研究的目的:
- 研究HCF-1和O-GlcNAcylation在肺癌发病过程中的作用.
- 探索HCF-1,OGT,O-GlcNAc和Nkx2.1在非小细胞肺癌 (NSCLC) 中的关系.
主要方法:
- 在人类肺癌组织中分析HCF-1,OGT,O-GlcNAc和Nkx2.1水平.
- 在NSCLC细胞系中进行HCF-1枯竭实验.
- 小麦胚芽聚合素 (WGA) 下拉测试以评估O-GlcNAcylated蛋白质.
- 在小鼠模型中,NKx2.1介导的HCF-1条件淘汰.
- 使用OSMI-1进行OGT抑制.
主要成果:
- 人类肺癌组织显示HCF-1,OGT,O-GlcNAc和Nkx2.1.1.的显著上调.
- 在NSCLC细胞中HCF-1的枯竭减少了增殖,O-GlcNAcylation和Nkx2.1的表达.
- 条件淘汰HCF-1损害了小鼠的肺部发育和扩散.
- OGT抑制降低了HCF-1,Nkx2.1水平和增殖,这表明O-GlcNAcylation在HCF-1信号传递中的作用.
结论:
- HCF-1和O-GlcNAcylation在肺癌的发病过程中起着至关重要的作用.
- 这些发现凸显了HCF-1和O-GlcNAcylation作为肺癌干预的潜在治疗点.
相关概念视频
Epigenetic Regulation
3.7K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.7K
Epigenetic Regulation
33.5K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.5K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
Induced Pluripotent Stem Cells
5.4K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
5.4K
Covalently Linked Protein Regulators
8.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.7K
Hedgehog Signaling Pathway
9.8K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.8K


