COPS5 regulates osteosarcoma progression by upregulating KHSRP to promote Per2 mRNA decay
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.COP9 signalosome subunit 5 (COPS5) drives osteosarcoma progression by promoting Period circadian clock 2 (Per2) mRNA decay via KH-type splicing regulatory protein (KHSRP). COPS5 inhibition suppressed tumor growth and malignant behaviors in osteosarcoma cells.
Area Of Science
- Oncology
- Molecular Biology
- Cell Biology
Background
- Osteosarcoma (OS) is a primary bone malignancy predominantly affecting children and adolescents.
- Understanding the molecular mechanisms driving OS progression is crucial for developing targeted therapies.
Purpose Of The Study
- To elucidate the regulatory role of COP9 signalosome subunit 5 (COPS5) in osteosarcoma (OS) pathogenesis.
- To investigate the interaction network of COPS5, KH-type splicing regulatory protein (KHSRP), and Period circadian clock 2 (Per2) in OS.
Main Methods
- Cell proliferation, migration, invasion, and apoptosis were assessed using CCK-8, wound healing, Transwell, and flow cytometry assays, respectively.
- Protein-protein interactions were confirmed via Co-immunoprecipitation (Co-IP) and GST-pull down assays.
- RNA-protein interactions were validated using RNA-pull down and RIP assays.
Main Results
- COPS5 knockdown significantly inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis.
- COPS5 knockdown also suppressed tumor growth in a xenograft mouse model.
- COPS5 directly interacted with KHSRP, stabilizing its protein levels.
- KHSRP was found to bind to Per2 mRNA, and COPS5 mediated KHSRP's decay effect on Per2 mRNA, thereby promoting OS tumorigenesis.
Conclusions
- COPS5 acts as a key oncogenic modulator in osteosarcoma.
- COPS5 promotes OS progression by stabilizing KHSRP and facilitating the decay of Per2 mRNA.
- Targeting the COPS5/KHSRP/Per2 axis presents a potential therapeutic strategy for osteosarcoma.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
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...
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...
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...
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...
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,...
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.
Three of the best-understood negative regulators are p53, p21, and retinoblastoma protein (Rb). The regulatory roles of each of these proteins were discovered after faulty copies were found in cells with uncontrolled replication (i.e.,...