综合性分析确定了非典型抑制剂E2F8作为可向的转录激活剂,驱动致命的前列腺癌
Furong Huang1, Kexin Li1, Zhong Chen1
1Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
Oncogene
|November 29, 2024
概括
研究人员确定E2F8是致死性前列腺癌的关键驱动因素,特别是在抗雄激素受体 (AR) 治疗的病例中. 准E2F8显示有望抑制晚期前列腺癌中瘤生长.
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:
- 获得对雄激素受体 (AR) 向疗法的耐药性是治疗致命前列腺癌的一个主要挑战.
- 确定新的治疗点对于改善割耐性前列腺癌 (CRPC) 的结果至关重要.
研究的目的:
- 在CRPC中选人类转录因子 (TFs) 的预后意义.
- 确定和描述AR阴性CRPC的新型治疗点.
主要方法:
- 分析来自西部和东部Stand Up to Cancer (SU2C) 队列的CRPC数据集,以评估1635个TFs.
- 在AR阴性CRPC细胞中的E2F8细胞体和转录体的整合分析.
- 使用CRISPR/CasRx系统进行E2F8mRNA淘汰.
主要成果:
- E2F8被确定为一种TF,与CRPC中患者的治疗结果较差的一致相关.
- 在AR阴性CRPC中,E2F8的表达和活性很高.
- E2F8直接激活参与癌症途径的瘤基因,其敲击抑制了CRPC在体外和体内生长.
结论:
- E2F8是一种可向的转录激活剂,驱动CRPC,特别是AR阴性CRPC.
- 准E2F8代表了晚期前列腺癌的潜在治疗策略.
相关概念视频
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Negative Regulator Molecules
35.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
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


