COPS5通过对KHSRP进行上调调节来调节骨髓瘤的进展,从而促进Per2 mRNA衰变
Jie Bu1, Xuezheng Xu1, Yi Luo1
1Department of Orthopaedics, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, Hunan Province, PR China.
Experimental cell research
|November 28, 2024
概括
COP9信号酶子单元5 (COPS5) 通过通过KH型拼接调节蛋白 (KHSRP) 促进昼夜时钟2 (Per2) mRNA衰变来驱动骨髓瘤的进展. 抑制COPS5抑制了骨髓瘤细胞中的瘤生长和恶性行为.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 骨髓瘤 (OS) 是一种主要影响儿童和青少年的骨恶性瘤.
- 了解驱动OS进展的分子机制对于开发向疗法至关重要.
研究的目的:
- 阐明COP9信号酶子单元5 (COPS5) 在骨髓瘤 (OS) 发病过程中的调节作用.
- 为了研究COPS5,KH型拼接调节蛋白 (KHSRP) 和周期昼夜时钟2 (Per2) 在OS中的相互作用网络.
主要方法:
- 分别使用CCK-8,伤口愈合,Transwell和流式细胞计量试验来评估细胞增殖,迁移,入侵和细胞亡.
- 通过共免疫沉 (Co-IP) 和GST-pull-down测定证实了蛋白质-蛋白质相互作用.
- 通过使用RNA-pull-down和RIP测定验证了RNA-蛋白相互作用.
主要成果:
- COPS5的淘汰显著抑制了OS细胞的增殖,迁移和入侵,同时促进了细胞亡.
- 在异种移植小鼠模型中,COPS5敲除也抑制了瘤生长.
- COPS5与KHSRP直接相互作用,稳定了其蛋白质水平.
- 发现KHSRP与Per2 mRNA结合,COPS5调解了KHSRP对Per2 mRNA的衰变效应,从而促进OS瘤发生.
结论:
- 在骨髓瘤中,COPS5作为关键的瘤调节器.
- COPS5通过稳定KHSRP并促进Per2mRNA的衰变来促进OS的进展.
- 准COPS5/KHSRP/Per2轴为骨髓瘤提供了一个潜在的治疗策略.
相关概念视频
03:03mTOR 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
02:23Abnormal Proliferation
4.5K
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...
4.5K
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
01:31Osteoclasts in Bone Remodeling
2.8K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.8K
01:20The Retinoblastoma Gene
4.1K
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,...
4.1K
01:23Negative 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