在清细胞细胞癌中,BMAL1和ARNT使昼夜HIF2α反应成为可能
Rebecca M Mello1,2, Diego Gomez Ceballos1,2, Colby R Sandate3
1Department of Molecular and Cellular Biology, Scripps Research Institute, La Jolla, CA, USA.
Nature communications
|July 2, 2025
概括
昼夜节律因子BMAL1,不仅仅是ARNT,与HIF2α合作,调节清细胞细胞癌 (ccRCC) 的生长. 针对这种BMAL1-HIF2α相互作用可能会改善ccRCC治疗灵敏度.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 时间生物学 时间生物学
背景情况:
- 昼夜干扰与癌症风险增加有关,许多瘤显示出改变的昼夜基因表达.
- 清细胞细胞癌 (ccRCC) 意外地显示出强大的节律基因表达.
- 核心昼夜转录因子BMAL1与已知HIF2α合作伙伴ARNT有相似之处.
研究的目的:
- 研究昼夜转录因子BMAL1在ccRCC中的作用.
- 为了确定BMAL1是否在ccRCC细胞中与HIF2α形成功能复合体.
- 探索ccRCC中的BMAL1-HIF2α相互作用的治疗含义.
主要方法:
- 使用分子生物学技术研究了ccRCC细胞中的BMAL1-HIF2α相互作用.
- 评估了BMAL1耗尽对HIF2α活性和ccRCC细胞生长在体外和体外异种移植中的影响.
- 对BMAL1表达和对HIF2α抗剂的敏感性分析了来自患者的异种移植数据.
- 评估了HIF2α抗剂疗效的每日时间依赖性.
主要成果:
- 在ccRCC中,BMAL1与HIF2α一起调节特定的一组HIF2α向基因.
- 减少BMAL1减少了HIF2α染色体结合,基因表达和ccRCC的生长.
- 较高的BMAL1水平与患者衍生异体移植中对HIF2α对抗剂PT2399的敏感性相关.
- BMAL1-HIF2α复合体对PT2399比ARNT-HIF2α复合体更敏感,药物的有效性取决于时间.
结论:
- 一种涉及昼夜蛋白BMAL1的替代HIF2α异构体影响HIF2α活性和ccRCC生长.
- 在ccRCC中,BMAL1-HIF2α通路是潜在的治疗点.
- 通过准BMAL1-HIF2α相互作用并考虑治疗时间,可以调节对ccRCC的药物疗效.
更多相关视频
05:36Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
9.1K
06:53Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
8.4K
相关概念视频
01:20The Retinoblastoma Gene
4.2K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
02:19Circadian Rhythms and Gene Regulation
4.2K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.2K
03:03mTOR Signaling and Cancer Progression
3.9K
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...
3.9K
02:23Abnormal 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