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Updated: Jun 29, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
USP5 promotes tumorigenesis by activating Hedgehog/Gli1 signaling pathway in osteosarcoma
Qing Wu1, Rui Liu2,3, Yuting Yang1
1Department of Orthopedics, The Second Affiliated Hospital of Nanchang University Nanchang 330006, Jiangxi, China.
Abstract:
Changes in protein ubiquitination have been linked to cancer. Deubiquitinating enzymes (DUBs) counteract E3 ligase activities and have emerged as promising targets for cancer treatment. Ubiquitin-specific peptidase 5 (USP5) is a member of the DUBs family and has been implicated in promoting tumorigenesis in numerous cancers. However, the clinical significance and biological function of USP5 in osteosarcoma (OS) remains unclear. Here, we found elevated USP5 expression in OS tissues compared with normal bone tissues. Furthermore, we observed significant associations of elevated USP5 levels with increased mortality and more malignant phenotypes in OS patients. Moreover, our results revealed that USP5 could facilitate metastasis and cell progression in OS by activating the hedgehog (Hh) signaling pathway using cultured cells and animal tumor models. Mechanistically, USP5 appeared to stabilize and deubiquitinate Gli1, a key mediator of the Hh signaling pathway. Additionally, the oncogenic effect of USP5 in OS was dependent on Gli1 stability. Our findings support the model where USP5 contributes to OS pathogenesis by activating the Hh/Gli1 signaling pathway, making USP5 a potential diagnostic and therapeutic target for OS.
Insights
Ubiquitin-specific peptidase 5 (USP5) promotes osteosarcoma (OS) progression by activating the hedgehog (Hh) signaling pathway. Elevated USP5 levels correlate with poor prognosis, suggesting USP5 as a potential therapeutic target for OS.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Protein ubiquitination is crucial in cancer development.
- Deubiquitinating enzymes (DUBs) are emerging cancer therapeutic targets.
- Ubiquitin-specific peptidase 5 (USP5) is implicated in various cancers, but its role in osteosarcoma (OS) is unknown.
Purpose of the Study:
- To investigate the clinical significance and biological function of USP5 in osteosarcoma.
- To elucidate the mechanism by which USP5 influences OS progression.
Main Methods:
- Analysis of USP5 expression in OS tissues and patient data.
- In vitro cell culture experiments and in vivo animal tumor models.
- Investigation of USP5's effect on the hedgehog (Hh) signaling pathway and Gli1 stability.
Main Results:
- USP5 expression is elevated in OS tissues and associated with increased mortality and malignancy.
- USP5 promotes OS cell metastasis and progression by activating the Hh/Gli1 pathway.
- USP5 stabilizes and deubiquitinates Gli1, mediating its oncogenic effects in OS.
Conclusions:
- USP5 plays a critical role in osteosarcoma pathogenesis by activating the Hh/Gli1 signaling pathway.
- USP5 is a potential diagnostic biomarker and therapeutic target for osteosarcoma.
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